LC column processing using a weighted counter

Abstract

The present invention relates to a method for operating a chromatographic column, which comprises: (a) providing a first value of the service life of the chromatographic column (first service life value); (b) performing chromatographic separation of a sample on the chromatographic column; (c) providing a value of a weighted aging factor determined based on at least one aging parameter selected from sample type, sample dilution, and sample volume; and (d) determining a second value of the service life of the chromatographic column (second service life value) based on the first service life value and the weighted aging factor. The present invention also relates to additional methods, databases, devices, and uses related thereto.

Description

[0001] The present invention relates to a method for operating a chromatographic column, which comprises: (a) providing a first value of the service life of the chromatographic column (first service life value); (b) performing chromatographic separation of a sample on the chromatographic column; (c) providing a value of a weighted aging factor determined based on at least one aging parameter selected from sample type, sample dilution, and sample volume; and (d) determining a second value of the service life of the chromatographic column (second service life value) based on the first service life value and the weighted aging factor. The present invention also relates to further methods, databases, devices, and uses related thereto.

[0002] LC columns generally have a service life predefined by the number of injections (a simple counter, as described in, for example, EP 2 880 437 A1). After reaching this number of injections, the column is no longer used. Alternatively, in some laboratories, the column can be used as long as the column performance is within the specified acceptable standards. Therefore, it has been proposed to estimate the service life of a device based on the time and temperature for which the device has been stored (US 8,279,072 B2). In addition, monitoring of chromatographic columns has been proposed based on the pressure of the column (EP 2 771 683 A1) or other output parameters (EP 2 338 049 A1).

[0003] By using a simple counter, the state of the column is not controlled, so columns with sufficient performance may still be excluded from further use. In addition, when using an LC column for a single determination, the use of a simple counter is limited. In addition, in random pick-and-place use, the use of a simple counter does not take into account differences in (for example) matrix loading in different determinations. This means that the maximum number of injections of the column must be defined by the most demanding determination in such cases, resulting in additional costs.

[0004] Conversely, when using a simple counter, even before reaching the maximum number of injections of the column, the column may no longer provide suitable performance for the target determination. In this case, although the performance of the column is insufficient, the column is not replaced, which may lead to incorrect results.

[0005] On the other hand, if the column service life is determined based on its performance, the column service life cannot be estimated, and thus the column replacement time cannot be planned.

[0006] The technical problem underlying the present invention can be seen as providing tools and methods that meet the aforementioned needs and avoid the identified problems as much as possible. The technical problem is solved by the features of the claims and the embodiments described hereinafter.

[0007] Accordingly, the present invention relates to a method for operating a chromatographic column, the method comprising

[0008] (a) Provide a first value of the service life of the column (first service life value);

[0009] (b) Perform chromatographic separation of a sample on the chromatographic column;

[0010] (c) Provide a value of a weighted aging factor determined based on at least one aging parameter selected from sample type, sample dilution, and sample volume; and

[0011] (d) Determine a second value of the service life of the chromatographic column (second service life value) based on the first service life value and the weighted aging factor.

[0012] Generally, the terms used herein are given their ordinary and customary meaning to those of ordinary skill in the art and are not limited to a special or custom meaning unless otherwise stated. As used below, the terms "having", "including", or "comprising" or any arbitrary grammatical variations thereof are used in a non-exclusive manner. Thus, these terms can refer both to cases where no other features exist in the entity described in this context except for the features introduced by these terms, and to cases where one or more other features exist. As an example, the statements "A has B", "A includes B", and "A comprises B" can refer both to cases where no other elements exist in A except for B (i.e., cases where A consists of B alone and uniquely), and to cases where one or more additional elements (such as element C, elements C and D, or even additional elements) exist in entity A in addition to B. Further, as understood by those skilled in the art, the expressions "comprising a" and "comprising one" preferably refer to "comprising one or more", i.e., are equivalent to "comprising at least one". As used herein, the term "plurality" refers to a number of at least two, in one embodiment at least three, in another embodiment at least four, in another embodiment at least five, in another embodiment at least ten.

[0013] In addition, as used below, the terms "preferably", "more preferably", "most preferably", "particularly", "more particularly", "specifically", "more specifically", or similar terms are used in conjunction with optional features without limiting other possibilities. Thus, the features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. As will be recognized by those skilled in the art, the present invention can be implemented by using alternative features. Similarly, features introduced by "in one embodiment" or similar expressions are intended to be optional features and have no limitation on other embodiments of the present invention, no limitation on the scope of the present invention, and no limitation on the possibility of combining the features introduced in this way with other optional or non-optional features of the present invention.

[0014] As used herein, unless otherwise indicated, the term "standard conditions" refers to IUPAC standard ambient temperature and pressure (SATP) conditions, i.e., preferably, a temperature of 25 °C and an absolute pressure of 100 kPa; equally preferably, standard conditions include a pH of 7. Further, unless otherwise stated, the term "about" refers to an indicated value with a technical precision recognized in the relevant art, preferably to an indicated value ±20%, more preferably ±10%, most preferably ±5%. Further, the term "substantially" means that there is no deviation that affects the indicated result or use, i.e., the potential deviation does not cause the indicated result to deviate by more than ±20%, more preferably ±10%, most preferably ±5%. Thus, "consisting essentially of" means including the specified components, but excluding other components, except for materials present as impurities, inevitable materials resulting from the process for providing the components, and components added for purposes other than achieving the technical effects of the present invention. For example, a composition defined using the phrase "consisting essentially of" encompasses any known acceptable additives, excipients, diluents, carriers, etc. Preferably, a composition consisting essentially of a group of components will contain less than 5% by weight, more preferably less than 3% by weight, even more preferably less than 1% by weight, most preferably less than 0.1% by weight of non-specified components.

[0015] The methods described herein are in vitro methods and, in one embodiment, at least one step is assisted or performed by an automated device. The entire method can also be implemented on such an automated device; for example, on a chromatography system. The steps can be performed in any order technically possible, however, in another embodiment, they are performed in a given order. Further, these methods can also include steps other than those explicitly mentioned above.

[0016] The term "chromatographic column" is understood by those skilled in the art. In one embodiment, the term refers to a container, typically cylindrical, that contains a stationary phase and has an inlet and an outlet for the mobile phase, which in one embodiment is a liquid or a gas, in another embodiment is a liquid, and in one embodiment is an aqueous chromatography solvent. In one embodiment, the chromatographic column is a liquid chromatography (LC) column, and in another embodiment is a high performance liquid chromatography (HPLC) or fast protein liquid chromatography (FPLC) column. Suitable stationary phase materials and mobile phases and their combinations are known in the art.

[0017] The term "operating a chromatographic column" is also understood by a person skilled in the art. In one embodiment, the term relates to performing chromatographic separation using a chromatographic column alone; in another embodiment, the term relates to performing a series of chromatographic separations using a chromatographic column, where the chromatographic separations may be separations according to the same protocol or according to different protocols. As described in more detail elsewhere herein, operating a chromatographic column may include operating the chromatographic column under a first protocol until a reference value of a second service life value is reached, after which, in a less demanding embodiment, operating the chromatographic column under a second protocol. As a person skilled in the art understands, the above-described protocol changes based on the second service life value may be repeated.

[0018] The term "chromatographic protocol", also referred to as "protocol", relates to the sum of the chromatographic parameters applied to a chromatographic column, i.e., in particular, the specific mobile phase or its gradient, temperature, pressure, flow rate, and sample type. As used herein, the term "assay" relates to the sum of the parameters defining the protocol, further including the chromatographic column to be used and the analysis to be performed, in particular one or more analytes to be determined, as well as sample preparation steps, such as those specified elsewhere herein. Thus, on a specific chromatographic column, in principle, the same protocol can be used to detect several different analytes, i.e., the same protocol is used for more than one different assay. However, different protocols can also be used to detect the same analyte. As can be clearly seen from the above, using different protocols to detect the same one or more analytes, and using the same protocol to detect different one or more analytes, each defines a specific assay in each case. In contrast, in embodiments independent of the protocol and / or assay, the term "separation" (which can also be referred to as "run") relates to a single event of performing chromatography using a specific chromatographic column. Nevertheless, the separation is typically performed using a specific protocol and in the context of a specific assay. In one embodiment, the chromatographic protocol includes eluent pH and pressure conditions.

[0019] As used herein, the term "eluent pH" relates to the pH of one or more eluents used in a chromatographic protocol, including any gradient thereof; as a person skilled in the art understands, the eluent pH is produced by a mixture of the mobile phase with different additives and buffers. In one embodiment, in a pick-and-place mode, the eluent pH value often varies and has a significant impact on column service life. For example, the silica-bonded stationary phase in an analytical column may wear at neutral to high pH values because the silica bonds are dissolved. This can lead to "column bleed" and a shortened column service life.

[0020] In one embodiment, the term "column backpressure" relates to the backpressure on a chromatographic column caused by the flow of the mobile phase from an HPLC pump and through the chromatographic column (e.g., to a detector). Column backpressure is typically measured by a pressure sensor between the HPLC pump head and the chromatographic column. In contrast, as used herein, the term "pressure conditions" in one embodiment relates to the backpressure expected on a particular column type when a particular protocol (in one embodiment at least the mobile phase (eluent) and flow rate) is applied to the particular column type; thus, the term "pressure conditions" in one embodiment does not relate to the backpressure measured or measurable on a particular column under its operating conditions (which is referred to as "column backpressure" as specified above). As will be understood by those skilled in the art, the pressure conditions for a particular protocol can, in one embodiment, be pre-determined by determining the column backpressure of the protocol on a specific type of chromatographic column (in one embodiment for at least one column of said type, in another embodiment for at least two columns of said type). In one embodiment, high pressure conditions can cause deformation of the stationary phase bed, especially at the inlet of the chromatographic column, and can result in reduced chromatographic performance and shortened column life. In one embodiment, high pressure conditions shorten the column life more than low backpressure. The pressure conditions on a chromatographic column are affected by parameters such as, for example, the flow rate of the mobile phase, the viscosity of the mobile phase, column dimensions, and particle size. In one embodiment, the viscosity of the mobile phase is affected by a gradient change in the organic solvent content and / or the type of organic solvent (e.g., a mixture of acetonitrile / water has a lower viscosity than a mixture of methanol / water). Column dimensions and particle size do not change, for example, during a random pick-and-place operating mode of the column, but the flow rate and viscosity can change frequently, thereby altering the pressure conditions.

[0021] The term "service life" of a chromatographic column refers to a parameter indicating the wear and tear of the chromatographic column due to separations previously performed thereon. In one embodiment, the service life is the remaining service life, i.e., a parameter indicating the number of separations that can be expected to be completed using the chromatographic column before the column performance becomes unacceptable; it should be understood that in such cases, the weighted aging factor and potentially additional factors are typically applied in a decreasing manner. In another embodiment, the service life is the used service life, i.e., a parameter indicating the number of separations that have been performed using the chromatographic column; it should be understood that in such cases, the weighted aging factor and potentially additional factors are typically applied in an increasing manner. Thus, in the case of the remaining service life, the service life can be indicated as the number of remaining runs, or in the case of the used service life, it can be the number of cumulative runs. However, it is also contemplated that the service life is an abstract value; for example, in an embodiment with arbitrary units, the service life can also be expressed as a calculated fraction of the initial performance or a service life score, or any other parameter that a person skilled in the art deems appropriate. As understood by a person skilled in the art, the service life of a chromatographic column is a column-specific parameter. In one embodiment, the service life of a chromatographic column is further a protocol-specific parameter and in one embodiment a determination-specific parameter; i.e., in one embodiment, different protocols, particularly determinations, differ in their requirements for column performance and thus the service life value can be different for different protocols and / or determinations. Thus, for a demanding determination, the chromatographic column may have reached the end of its remaining service life, but it may still be usable for a less demanding determination. In one embodiment, the determination of the first service life parameter and the second service life parameter is as specified below.

[0022] In one embodiment, the value of the first service life parameter is the value of the initial service life of the chromatographic column ("initial service life value"), i.e., in one embodiment, the service life value of the chromatographic column before the first run. The initial service life value can be provided by the manufacturer of the chromatographic column, can be based on the experience of similar chromatographic columns, and / or can be determined experimentally. The initial service life value can be further corrected for the individual characteristics of the specific column and / or the specific protocol and / or determination for which the column is planned to be used. As understood by a person skilled in the art from the foregoing, the initial service life value is in one embodiment a column type-specific value, in one embodiment a column-specific value and / or a protocol-specific value, and in one embodiment a determination-specific value. Thus, if the protocol (in one embodiment, the determination) for using the chromatographic column changes, the initial service life value may also change.

[0023] The second service life value provided is as specified below. In one embodiment, the second service life value is the current service life value, i.e., the service life value applicable immediately after the previous separation.

[0024] As used herein, the term "aging parameter" relates to any parameter that causes column wear and thus affects the column service life. In one embodiment, the aging parameter is a quantitative parameter, i.e., a parameter that can be quantified, such as sample dilution. In another embodiment, the aging parameter is a semi-quantitative or qualitative parameter, i.e., a parameter that cannot be quantified or is impractical to quantify, such as sample matrix. In such cases, in one embodiment in all cases, the aging parameters are divided into different categories ("aging parameter categories") and a numerical value is assigned to each category, where the assigned numerical value ("aging parameter factor") is related to the effect of the category on the column service life. Thus, the aging parameter can include a category descriptor and an assigned aging parameter factor. Accordingly, the specification of the aging parameter (e.g., in a database) can, in one embodiment, include aging parameter categories such as "whole blood", "serum", "plasma", "saliva", etc. as descriptors of the sample matrix, and / or categories such as "unpurified", "solvent-precipitated", "affinity-purified", etc. as descriptors of the purification status, with the numerical values assigned to the aging parameter factor in each case. For other aging parameters, especially for quantifiable aging parameters, the actual value or a value derived therefrom by standard mathematical operations can be used as the aging parameter category. For example, in one embodiment, the value of the sample dilution can be used in this way; and / or the reciprocal of the sample volume value can be used. Thus, in the case of quantifiable aging parameter categories, the aging parameter category and the aging parameter factor can have the same value; or the aging parameter can only be assigned one (numerical) value. However, especially in cases where the correlation between the aging parameter and the service life is disproportionate, for the assignment of the aging parameter category and the assigned aging parameter factor, it is conceivable that the aging parameter category and the assigned aging parameter factor have different numerical values. In one embodiment, the aging parameter category can also be a range of values (especially numerical values). In one embodiment as specified below, the aging parameter factor can be provided in any way considered appropriate by a person skilled in the art. In one embodiment, the aging parameter factor can be determined experimentally by performing test separations under conditions including the respective one or more aging parameters and determining the effect on the column service life. In one embodiment, the one or more aging parameter factors are determined in connection with the actual use of the column, for example by determining one or more performance parameters. In one embodiment, the aging parameter is a parameter of a particular type of sample used in a particular assay, and thus, in one embodiment, can be provided in a database as specified below; thus, in one embodiment, the aging parameter is not a parameter specific to an individual sample.In one embodiment, the aging parameters are selected from the list consisting of sample type, sample dilution, sample volume, time since last use, storage conditions since last use, and chromatographic conditions applied, wherein, in one embodiment, the group of chromatographic conditions includes some or all of the conditions defining the chromatographic protocol, and optionally a parameter indicating whether a solvent change is required. Thus, in one embodiment, the aging parameters are sample-specific aging parameters, particularly selected from sample type, sample dilution, and sample volume; or are operation-specific parameters, particularly assay-specific parameters, time since last use, storage conditions since last use, and / or a parameter indicating whether a solvent change is required, wherein the assay-specific aging parameters can particularly be eluent pH and / or pressure conditions.

[0025] The term "performance parameter" is in principle known to the person skilled in the art and includes any measurable parameter indicating the suitability of the chromatographic column for the separation purpose. In one embodiment, the performance parameters are selected from the list consisting of retention time of the analyte, peak width, peak symmetry, resolution, breakthrough point, and column pressure. In one embodiment, at least one of the above performance parameters is determined online during the use of the chromatographic column.

[0026] As used herein, the term "sample type" includes every parameter affecting the type and content of the sample components. In one embodiment, the sample type is defined at least by the sample matrix and the pre-purification state of the sample. The known term "sample matrix" relates to all non-analyte components of the sample; in one embodiment, the sample matrix is defined by the sample source, for example, in one embodiment, it is a body fluid sample, such as whole blood, serum, plasma, urine, saliva, or sputum; or it is a tissue sample, such as biopsy material. The "pre-purification state" of the sample relates to all measures applied to the sample after obtaining the sample, which at least partially remove sample components, particularly matrix components. Pre-purification steps are known in the art and particularly include centrifugation, precipitation, solvent treatment, extraction, homogenization, heat treatment, freezing and thawing, cell lysis, application to a pre-column, etc., as specified elsewhere herein in one embodiment. It should be understood from the above that, as used herein, any difference in the pre-purification steps that results in different sample components is, in one embodiment, considered to provide different sample types; thus, for example, a serum sample centrifuged at low speed and a serum sample centrifuged at high speed may be different sample types.

[0027] The term "sample dilution" is used herein in its conventional meaning, as are the terms "sample volume", "time since last use", and "storage conditions since last use", wherein the storage conditions since last use particularly include storage temperature in one embodiment.

[0028] As used herein, the term "set of chromatographic conditions" refers to a subset or complete set of chromatographic conditions that define a protocol as specified above; in one embodiment, for example, performing chromatography at a temperature of 60 °C may have a different impact on the column lifetime compared to performing the same protocol at a temperature of 4 °C. In one embodiment, the set of chromatographic conditions includes some or all of the conditions that define a chromatographic protocol, and optionally a parameter indicating whether a solvent change is required.

[0029] As used herein, the term "solvent change" refers to the replacement of the mobile phase in a chromatographic pump (in one embodiment, in the pump head). In a pick-and-place operation mode of the chromatographic column, different assays may require different mobile phase mixtures. It may be necessary to remove the mixture from the previous run from the pump head and pump the next mobile phase mixture. During this solvent change process, no mobile phase flows to the column, which in one embodiment results in a sudden drop in backpressure, and at the end of the process, in one embodiment, as the new mobile phase is pumped onto the chromatographic column, there is a sudden increase in backpressure at the analytical head. The sudden drop and increase in pressure ("pressure shock") may cause deformation of the stationary phase bed in the chromatographic column and may shorten the column lifetime with each solvent change process.

[0030] As used herein, the term "aging factor" refers to a parameter indicating the change in chromatographic column lifetime caused by one or more chromatographic separations. The value of the aging factor depends on how the lifetime parameter is provided; for example, if the lifetime is provided as the remaining lifetime in terms of the remaining number of chromatographic runs, the aging factor can be a subtractive number. Conversely, if the lifetime is provided as the used lifetime (e.g., the number of runs that have been performed), the aging factor can be an additive number. As described above, the lifetime can also be provided as different parameters, such as as a percentage or score of the total lifetime. It should be understood from the above that the term "factor" related to the aging factor or weighted aging factor is not necessarily related to a mathematical factor in multiplication, although this may be the case, but the factor is a factor that contributes to the calculation of aging, and it can also be, for example, an additive number, a subtractive number, or a divisor.

[0031] As used herein, the term "weighted aging factor" refers to an aging factor that is adjusted for wear based on specific conditions or a set of conditions applied to a chromatographic column, particularly aging parameters such as sample type, sample dilution, and / or sample volume. Thus, the weighted aging factor corresponds to an aging factor modified according to the value of at least one applicable aging parameter. Thus, for example, if one or more applicable aging parameters are known to cause increased column wear, the weighted aging factor may be higher than the aging factor. Aging parameter values known to contribute to increased wear include, for example, high complexity of the sample matrix (e.g., in blood samples), low degree of pre-purification (e.g., direct use of serum samples), low sample dilution, and / or large sample volume. Conversely, for example, if one or more applicable aging parameters are known to cause decreased column wear, the weighted aging factor may be lower than the aging factor; aging parameter values known to contribute to decreased wear include, for example, low complexity of the sample matrix (e.g., in urine samples), high degree of pre-purification (e.g., in affinity-purified samples), high sample dilution, and / or small sample volume. As will be understood by those skilled in the art, the weighted aging factor is not necessarily based on the (theoretical) aging factor, and thus providing the aging factor is not necessarily required in all cases to provide the value of the weighted aging factor. Thus, in one embodiment, the weighted aging factor is calculated directly based on the values assigned to the corresponding one or more aging parameters, which may be provided experimentally and stored in a database. As an example, if the remaining run time of the chromatographic column is provided as the service life, the weighted aging factor may be >1 if one or more applicable aging parameters are known to cause increased wear; the weighted aging factor may be <1 if one or more applicable aging parameters are known to cause decreased wear; and the weighted aging factor may be approximately 1 if one or more applicable aging parameters are known to cause average wear. In one embodiment, a separate value is provided for each aging parameter, e.g., for the sample matrix, sample pre-purification status, and sample dilution, based on which the weighted aging parameter is calculated. In another embodiment, a common weighted aging parameter may be provided for a set of specific aging parameters, e.g., for a type of sample used in an assay, such as a common weighted aging parameter for undiluted, unpre-purified serum samples; correspondingly, it is also contemplated that a common weighted aging parameter is provided for an assay in one embodiment. Additionally, in one embodiment, the weighted aging parameter is calculated for a specific run on the chromatographic column. In another embodiment, the aggregated weighted aging parameter is calculated for multiple (in another embodiment, all) previous runs on the chromatographic column.

[0032] As used herein, the term "sample", also referred to as "test sample", relates to any type of substance composition; thus, the term can refer to, but is not limited to, any arbitrary sample, such as a biological sample. In one embodiment, the sample is a liquid sample, and in a further embodiment, an aqueous sample. In one embodiment, the test sample is optionally selected from the group consisting of: physiological body fluids, including whole blood, serum, plasma, saliva, aqueous humor of the eye, tears, cerebrospinal fluid, sweat, urine, milk, ascites, mucus, synovial fluid, peritoneal fluid, and amniotic fluid; lavage fluids; tissues, cells, etc. However, the sample can also be a natural or industrial liquid, particularly surface water or groundwater, sewage, industrial wastewater, process fluids, soil eluates, etc. In one embodiment, the sample comprises or is suspected of comprising at least one target chemical compound, i.e., the chemical substance to be determined, which is referred to as the "analyte". The sample can comprise one or more additional chemical compounds that are not determined and are generally referred to as the "matrix", as specified above. The sample can be used directly upon obtaining from the corresponding source, or can be subjected to one or more pre-treatment and / or sample preparation steps. Thus, the sample can be pre-treated by physical and / or chemical methods, in one embodiment by centrifugation, filtration, mixing, homogenization, chromatography, precipitation, dilution, concentration, contact with binding and / or detection reagents, and / or any other method considered appropriate by a person skilled in the art. In the sample preparation step, i.e., before, during, and / or after the sample preparation step, one or more internal standards can be added to the sample. The sample may be spiked with internal standards. For example, the internal standard can be added to the sample at a predefined concentration. The internal standard can be selected such that it is easily identifiable under the normal operating conditions of the selected detector (e.g., a mass spectrometry device, a photometric cell (e.g., in an ultraviolet-visible spectroscopy device), an evaporative light scattering refractometer, a conductivity meter, or any device considered appropriate by a person skilled in the art). The concentration of the internal standard can be predetermined and significantly higher than the concentration of the analyte.

[0033] As described above, the term "analyte" as used herein refers to any chemical compound or group of compounds to be determined in a sample. In one embodiment, the analyte is a macromolecule, i.e., a compound having a molecular mass greater than 1000 u (i.e., greater than 1 kDa). In a further embodiment, the analyte is a biological macromolecule, in particular a polypeptide, polynucleotide, polysaccharide or fragment of any of the foregoing. In one embodiment, the analyte is a small molecule chemical compound, i.e., a compound having a molecular mass of at most 1000 u (1 kDa). In a further embodiment, the analyte is a compound metabolized by the body of a subject, in particular a human subject, or a compound administered to a subject to induce a change in the subject's metabolism. Thus, in one embodiment, the analyte is a prohibited drug or its metabolite, such as amphetamine; cocaine; methadone; ethyl glucuronide; ethyl sulfate; opium, in particular buprenorphine, 6-monoacetylmorphine, codeine, dihydrocodeine, morphine, morphine-3-glucuronide and / or tramadol; and / or an opioid, in particular acetylfentanyl, carfentanil, fentanyl, hydrocodone, norfentanyl, oxycodone and / or oxymorphone.

[0034] In one embodiment, the analyte is a therapeutic drug, such as valproic acid; clonazepam; methotrexate; voriconazole; mycophenolic acid (total); mycophenolic acid - glucuronide; acetaminophen; salicylic acid; theophylline; digoxin; immunosuppressants, especially cyclosporine, everolimus, sirolimus and / or tacrolimus; analgesics, especially pethidine, norpethidine, tramadol and / or O - desmethyltramadol; antibiotics, especially gentamicin, tobramycin, amikacin, vancomycin - resistant, piperacillin (tazobactam), meropenem and / or linezolid; antiepileptic drugs, especially phenytoin sodium, valproic acid, free phenytoin sodium, free valproic acid, levetiracetam, carbamazepine, carbamazepine - 10,11 - epoxide, phenobarbital, primidone, gabapentin, zonisamide, lamotrigine and / or topiramate. In one embodiment, the analyte is a hormone, especially cortisol, estradiol, progesterone, testosterone, 17 - hydroxyprogesterone, aldosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA - S), dihydrotestosterone and / or cortisone; in one embodiment, the sample is a serum or plasma sample and the analyte is cortisol, DHEA - S, estradiol, progesterone, testosterone, 17 - hydroxyprogesterone, aldosterone, DHEA, dihydrotestosterone and / or cortisone; in one embodiment, the sample is a saliva sample and the analyte is cortisol, estradiol, progesterone, testosterone, 17 - hydroxyprogesterone, androstenedione and / or cortisone; in one embodiment, the sample is a urine sample and the analyte is cortisol, aldosterone and / or cortisone. In one embodiment, the analyte is a vitamin, in one embodiment vitamin D, especially ergocalciferol (vitamin D2) and / or cholecalciferol (vitamin D3) or its derivatives, such as 25 - hydroxy - vitamin - D2, 25 - hydroxy - vitamin - D3, 24,25 - dihydroxy - vitamin - D2, 24,25 - dihydroxy - vitamin - D3, 1,25 - dihydroxy - vitamin - D2 and / or 1,25 - dihydroxy - vitamin - D3. In a further embodiment, the analyte is a metabolite of the subject.

[0035] Operating a chromatographic column includes step (a) of providing a first value of the service life of the chromatographic column (first service life value). As used herein, the term "providing a first service life value" relates to any way of obtaining the value. In one embodiment, the first service life value is determined based on an initial service life value or a corrected initial service life value, as specified above. In one embodiment, the first service life value is based on (in another embodiment is) the service life value effective for the chromatographic column at the end of the previous (in one embodiment the immediately previous) separation, i.e., the previous service life value. Thus, if the chromatographic column is used for a series of chromatographic separations, the second service life value of the immediately previous separation as specified herein can be the first service life value for the current separation. In another embodiment, the initial service life value is provided based on the initial service life value as specified above, which has been corrected according to the cumulative service life impact of all or part of the previous separations; in such cases, it may not be necessary to provide the previous service life value. In one embodiment, the first service life value of the column is based on the initial value of the service life and a weighted aging factor for any previous use of the chromatographic column. In one embodiment, if the initial service life value and the previous service life value are not available, an estimated first service life value can be provided based on, for example, one or more performance parameters of the chromatographic column (preferably as specified below).

[0036] Operating the chromatographic column further includes step (b) of performing a chromatographic separation of a sample on the chromatographic column. In one embodiment, the step includes applying the sample and at least one column void volume (in another embodiment, at least one column volume) of the mobile phase to the chromatographic column. This step may further include the steps of applying additional mobile phase, a mobile phase gradient, and / or applying re-equilibration to the chromatographic column. Additionally, this step may include detecting one or more analytes after separation by a manner known to those skilled in the art, and / or collecting one or more fractions for further analysis. This step may also include performing mass spectrometry on at least a portion of the eluate from the chromatographic column.

[0037] Operating the chromatography column further comprises the step (c) of providing a value of a weighted aging factor calculated based on at least one aging parameter selected from sample type, sample dilution, and sample volume. The terms "aging parameter" and "weighted aging factor" are specified above. In one embodiment, the value of the weighted aging factor is calculated based on aging parameters including sample type, sample dilution, and sample volume; in another embodiment, the value of the weighted aging factor is calculated based on aging parameters including sample type, sample dilution, sample volume, and the set of chromatographic conditions applied. In one embodiment, the aging parameters are combined into a single assay-specific weighted aging factor. As described above, the aging parameters can be quantifiable and have such values, or can have assigned aging parameter factor values. Thus, in one embodiment, calculating the weighted aging factor comprises providing the value of the aging parameter or the aging parameter factor assigned thereto, e.g., in one embodiment, from a database. Based on the numerical value of the aging parameter or the aging parameter factor assigned thereto, the weighted aging factor can in principle be calculated in any way considered appropriate by a person skilled in the art; thus, based on the information provided herein, a person skilled in the art is able to calculate a weighted aging factor considered appropriate. In an exemplary embodiment, the aging parameters sample type, sample dilution, and sample volume are determined. In such cases, the weighted aging factor (F) for a single separation can be calculated according to equation (1):

[0038] F = T × D × V (1)

[0039] where T = sample type aging parameter; D = sample dilution aging parameter; and V = sample volume aging parameter. Additionally, the weighted aging factor (F) for several separations can be calculated according to equation (2):

[0040]

[0041] where Ti = sample type aging parameter for chromatographic separation i; Di = sample dilution aging parameter for chromatographic separation i; Vi = sample volume aging parameter for chromatographic separation i; n = total number of chromatographic separations performed on the column. As will be understood by a person skilled in the art, the aging parameter factor value assigned to an aging parameter (e.g.) can also be expressed as a fraction of the total service life in one embodiment; thus, in such cases, the weighted aging factor can be calculated as the sum of the individual aging parameter values.

[0042] In view of the above, the present invention relates to a method for operating a chromatography column, the method comprising

[0043] (a) providing a first value of the service life of the column (first service life value);

[0044] (b) performing a chromatographic separation of a sample on the chromatography column;

[0045] (c) providing a value of a weighted aging factor determined based on at least one sample-specific aging parameter selected from sample type, sample dilution, and sample volume and based on at least one operation-specific aging parameter; and

[0046] (d) determining a second value (second service life value) of the service life of the chromatographic column based on the first service life value and the weighted aging factor.

[0047] In one embodiment, operating the chromatographic column further includes step (c) of providing a value of a weighted aging factor calculated based on at least one aging parameter selected from sample type, sample dilution, and sample volume and based on at least one operation-specific aging parameter. The terms "aging parameter" and "weighted aging factor" are specified above. In one embodiment, the value of the weighted aging factor is calculated based on sample-specific aging parameters including sample type, sample dilution, and sample volume and operation-specific aging parameters including eluent pH, pressure conditions, and a parameter indicating solvent change; in another embodiment, the value of the weighted aging factor is calculated based on aging parameters including sample type, sample dilution, sample volume, and a set of applied chromatographic conditions. In one embodiment, the sample-specific aging parameters and the assay-specific aging parameters are combined into a single, assay-specific weighted aging factor. As described above, the aging parameter can be quantifiable and have such a value, or an aging parameter factor value can be assigned to it. Thus, in one embodiment, calculating the weighted aging factor includes providing the value of the aging parameter or the aging parameter factor value assigned to it, e.g., from a database in one embodiment. Based on the numerical value of the aging parameter or the aging parameter factor assigned to it, the weighted aging factor can in principle be calculated in any way considered appropriate by a person skilled in the art; thus, based on the information provided herein, a person skilled in the art is able to calculate a weighted aging factor considered appropriate. In an exemplary embodiment, the aging parameters sample type, sample dilution, and sample volume are determined. In such cases, the weighted aging factor (F) for one separation can be calculated according to equation (10):

[0048] F = T × D × V × E × P × S (10)

[0049] where T = sample type aging parameter; D = sample dilution aging parameter; V = sample volume aging parameter; E = eluent pH aging parameter; P = pressure conditions aging parameter; S = solvent change aging parameter. Additionally, the weighted aging factor (F) for several separations can be calculated according to equation (11):

[0050]

[0051] where T i= Aging parameter of the sample type for chromatographic separation i; D i = Aging parameter of the sample dilution for chromatographic separation i; V i = Aging parameter of the sample volume for chromatographic separation i; E i = Aging parameter of the eluent pH for chromatographic separation i; P i = Aging parameter of the pressure condition for chromatographic separation i; S i = Aging parameter of the solvent replacement for chromatographic separation i, and n = total number of chromatographic separations performed on the column. As understood by those skilled in the art, the aging parameter factor values assigned to the aging parameters (for example) can also be expressed as a fraction of the total service life in one embodiment; thus, in such cases, the weighted aging factor can be calculated as the sum of the respective aging parameter values.

[0052] Operating the column further includes step (d) of determining a second value (second service life value) of the service life of the column based on the first service life value and the weighted aging factor. The determination of the second service life value can in principle be accomplished by any method considered appropriate by those skilled in the art, and in particular the method is selected according to the form of the provided first service life value and weighted aging factor. Thus, if the first service life value is the remaining service life value, the weighted aging factor will typically be applied such that separations that cause a reduction in the column service life result in a second service life value lower than the first service life value. In an exemplary embodiment, the second service life value (R L ) is calculated according to Equation (3):

[0053] R L = R L-1 - F(3)

[0054] where R L-1 = First service life value; and F = weighted aging factor.

[0055] Conversely, if the first service life value is the used service life value, the weighted aging factor will typically be applied such that separations that cause a reduction in the column service life result in a second service life value higher than the first service life value. Thus, in another exemplary embodiment, the second service life value (R L ) is calculated according to Equation (4):

[0056] R L = R L-1 + F(4)

[0057] where R L-1 = First service life value; and F = weighted aging factor.

[0058] In another exemplary embodiment, determining the second service life value may also be based on the initial service life value (R0) and the cumulative weighted aging factor; thus, if the remaining service life is to be determined based on the initial service life, it can be calculated according to Equation (5):

[0059]

[0060] where Fi = the weighted aging factor for chromatographic separation i; n = the total number of chromatographic separations performed on the column. Thus, the second service life value can be provided as the remaining service life, which is according to Equation (6)

[0061]

[0062] where defined as above.

[0063] Conversely, if the service life used in multiple separations is to be determined, it can be according to Equation (7)

[0064]

[0065] or Equation (8)

[0066]

[0067] where defined as above. As those skilled in the art will understand, if the service life of the column during its entire use is to be determined, R0 can be 0.

[0068] Optionally, determining the second service life value in step b) is further based on at least one of the following: (i) a parameter indicating the initial performance of the column, which is determined in an embodiment during the factory test; (ii) a parameter indicating the performance requirement of the target determination; (iii) a parameter indicating the current performance of the column; and (iv) a parameter indicating column load aging, which is in an embodiment the time and / or temperature held by the column.

[0069] As used herein, the term "parameter indicating the initial performance of the column" includes all measurable parameters related to the initial column performance (i.e., the column performance before the first separation is performed). Accordingly, the parameter indicating the initial performance is determined before the first separation is performed, in an embodiment during the factory test. Suitable parameters are in particular the performance parameters as specified above. As those skilled in the art will understand, even for newly manufactured columns of the same type, there is some individual variability in their performance; thus, including the parameter indicating the individual initial performance of the column in determining the second service life value compensates for this initial variability. The parameter indicating the initial performance can also be used to correct the initial service life value, for example, the initial service life value provided by the column manufacturer.

[0070] The term "parameter indicating the performance requirements of the target determination" relates to parameters associated with the performance requirements of a specific determination. As described above, different determinations may have different requirements for column performance. Also as described above, the requirements may be reflected by the definition of determination-specific reference values; alternatively or additionally, the requirements may also be reflected by including parameters indicating the performance requirements in the determination of the second service life value. Thus, if (for example) a remaining service life is provided, parameters indicating the performance requirements of the determination may be selected to reduce the value of the resulting second service life value in the case of a determination that requires high performance. Thus, in one embodiment, the parameter indicating the performance requirements is a parameter of a planned subsequent determination.

[0071] The term "parameter indicating the current performance of the column" is understood by the person skilled in the art and particularly includes the performance parameters specified above. In one embodiment, the parameter indicating the current performance is determined after at least one separation has been performed on the column, and in another embodiment during and / or after the immediately preceding and / or current separation.

[0072] As used herein, the term "parameter indicating column loading aging" includes any parameter related to column aging independent of the separation performed on the column. Thus, the term particularly relates to environmental factors that have an impact on the column expiration date, which in one embodiment is the time and / or temperature at which the column is held.

[0073] According to the above, in one embodiment, if a remaining service life value is provided, the second service life value of the column for the target determination is according to Equation (9)

[0074]

[0075] wherein it is defined as above, and additionally defined as: γ = parameter indicating the initial performance of the column; β = parameter indicating the performance requirements of the target determination; δ = parameter indicating the current performance of the column; ε = parameter indicating column loading aging; t n = the time point at which the second service life value is determined; and t0 = the time point at which the column is first used.

[0076] Optionally, operating the chromatographic column further comprises a step (e) of comparing the second service life value with a reference value. As used herein, the term "reference value" refers to a service life value that is pre-determined or is considered to represent a service life value that ensures that the chromatographic column is still suitable for a given assay. Thus, in one embodiment, the reference value is a threshold or range that is considered or has been determined to be such that the performance of the chromatographic column is sufficient to achieve the purpose of the assay (meeting applicable quality standards in one embodiment). Thus, the use of the chromatographic column can be stopped or modified based on the result of the comparison step (e). In one embodiment, if the second service life value is outside a predefined reference range or exceeds a reference threshold, the use of the chromatographic column is stopped or modified. In an exemplary embodiment, if the service life value is provided as a remaining service life value, the use of the chromatographic column is stopped or modified when it is found that the second service life value is below the reference value (e.g., a pre-determined threshold) or outside a pre-determined reference range.

[0077] Based on the result of step (e), the use of the chromatographic column can be continued, stopped, or modified. It should be understood from the above that if the comparison in step (e) indicates that the chromatographic column is still suitable for achieving the purpose of the assay, the chromatographic column can be continued to be used in the assay. If the comparison in step (e) indicates that the chromatographic column is no longer suitable for achieving the purpose of the assay, the use of the chromatographic column can be stopped in the assay or the use of the chromatographic column can be modified. In one embodiment, the modification of the use of the chromatographic column includes measures to improve column performance, such as including re-packing the chromatographic column and / or applying in-situ cleaning measures; as understood by a person skilled in the art, measures to improve column performance may have an impact on the value of the column service life; for example, if the service life value is provided as a remaining service life value, the remaining service life value may be increased by such measures. In another embodiment, the modification of the use of the chromatographic column includes reserving the chromatographic column for applications where lower performance is required. Thus, in one embodiment, the reference value as specified herein is a value specific to the assay.

[0078] In one embodiment, the method for operating the chromatographic column is a predictive method, and / or in one embodiment, the aging parameter value is pre-determined. Thus, in one embodiment, the method can be fully performed during the normal operation of the column and particularly does not require supplementary runs or runs using labeled compounds in the absence of samples to determine the service life of the chromatographic column. Thus, using the method of the present invention, in one embodiment, it is advantageously possible to avoid having to intersperse control runs to ensure column performance between analytical runs. However, it is conceivable to intersperse such control runs, for example, after every 100 runs, to determine a new first value of the column service life.

[0079] In one embodiment, the method for operating a chromatographic column is part of a method for predicting the end time of column availability, which may include performing the method for operating a chromatographic column as specified herein at least twice, and in one embodiment using the second service life value determined after the first execution of the method as the first service life value for the second execution of the method. As understood by those skilled in the art, the above procedure may be performed several times, thereby providing, for example, a series of remaining service life values that decrease with the number of chromatographic separations, thus allowing the reference service life value to be extrapolated by standard mathematical methods.

[0080] Advantageously, it has been found in the fundamental work of the present invention that the operation of the chromatographic column can be improved by the procedures specified herein; in particular, the column performance can be better predicted by using a weighted aging factor. Additionally, the quality control requirements can be better met by the methods described herein.

[0081] The definitions made above apply mutatis mutandis to the following. The additional definitions and explanations made below also apply mutatis mutandis to all embodiments described in this specification.

[0082] The present invention also relates to a method for operating a chromatographic column, which method comprises

[0083] (a) providing an initial value of the service life of the chromatographic column (initial service life value);

[0084] (b) performing a chromatographic separation of a sample on the chromatographic column;

[0085] (c) providing a parameter value indicating the initial performance of the chromatographic column based on the chromatographic separation of step (b); and

[0086] (d) determining a corrected initial value of the initial service life of the chromatographic column (corrected initial service life value) based on the initial service life value and the parameter indicating the initial performance of the chromatographic column.

[0087] The present invention also relates to a method for operating a chromatographic column, which method comprises

[0088] (a) providing a first value of the service life of the chromatographic column (first service life value);

[0089] (b) providing a parameter value indicating the performance requirements of the target determination; and

[0090] (c) determining a second value of the service life of the chromatographic column (second service life value) based on the first service life value and the value of the parameter indicating the performance requirements of the target determination.

[0091] The present invention also relates to a method for operating a chromatographic column, which method comprises

[0092] (a) Provide a first value (first service life value) of the service life of the chromatographic column;

[0093] (b) Perform chromatographic separation of a sample on the chromatographic column;

[0094] (c) Provide a parameter value indicating the current performance of the chromatographic column based on the chromatographic separation in step (b); and

[0095] (d) Determine a second value (second service life value) of the service life of the chromatographic column based on the first service life value and the value of the parameter indicating the current performance of the chromatographic column.

[0096] The present invention further relates to a method for operating a chromatographic column, the method comprising

[0097] (a) Provide a first value (first service life value) of the service life of the chromatographic column;

[0098] (b) Provide a parameter value indicating column carrier aging; and

[0099] (c) Determine a second value (second service life value) of the service life of the chromatographic column based on the first service life value and the value of the parameter indicating column carrier aging.

[0100] As described above, a general weighted aging factor can be provided for the determination. As those skilled in the art will understand, such a general weighted aging factor can be provided by a method comprising the following steps:

[0101] (I) Determine at least one first value of the performance parameter of the chromatographic column;

[0102] (II) Perform at least one, preferably multiple, chromatographic separations under the determination conditions;

[0103] (III) Determine at least one second value of the performance parameter; and

[0104] (IV) Determine the value of the general weighted aging parameter for the determination based on the first performance parameter and the second performance parameter or the value derived therefrom.

[0105] The present invention further relates to a method for establishing a data set of annotated aging parameter categories and aging parameter factors for the aging parameter value of a chromatographic column, the data set being preferably tangibly embedded on a storage medium, the method comprising

[0106] (I) Determine at least one first value of the performance parameter of the chromatographic column;

[0107] (II) Perform at least one, preferably multiple, chromatographic separations under the condition of a first set of aging parameter category values;

[0108] (III) Determine at least one second value of the performance parameter;

[0109] (IV) Perform at least one, preferably multiple chromatographic separations under the conditions of a second set of aging parameter category values; wherein the second set of aging parameter category values is different from the first set of aging parameter category values;

[0110] (V) Determine at least one third value of the performance parameter; and

[0111] (VI) Based on the first performance parameter, the second performance parameter, and the third performance parameter or values derived therefrom; and the first set of aging parameter category values and the second set of aging parameter category values or values derived therefrom, determine the value of the aging parameter factor of at least one aging parameter category, and annotate the value of the at least one aging parameter category and the value of the aging parameter factor to the data set.

[0112] The above method for establishing a data set of the present invention may include additional steps, such as determining additional values of the performance parameter under the conditions of another set of aging parameter category values different from the first set and the second set of aging parameter category values. Additionally, one or more steps (in one embodiment, all steps) are assisted or performed by an automated device. Further, the method may include determining at least one analyte, that is, the method may be an online method performed simultaneously with performing a chromatographic determination on a chromatographic column. Thus, in one embodiment, the method may further include collecting the values of the performance parameter during the use of at least one analytical system with the chromatographic column. In one embodiment, the method further includes collecting the information through a plurality of analytical systems. In one embodiment, the values of the data collection established as specified above are considered applicable to all chromatographic columns of a specific batch, in another embodiment, applicable to all chromatographic columns of a specific column configuration (such as may be represented by, for example, the manufacturer and order number or type name), and in another embodiment, applicable to all chromatographic columns of a specific column type. Thus, the method for establishing a data set may be performed on more than one chromatographic column; as those skilled in the art will understand, in such cases, it may be necessary to perform steps (III) on each column. Thus, in one embodiment, steps (I) to (III) may be performed on a first chromatographic column or group of chromatographic columns, and steps (III) to (V) may be performed on a second chromatographic column or group of chromatographic columns. In one embodiment, in such cases, the first chromatographic column and the second chromatographic column are from the same batch, the same column configuration, and / or the same column type.

[0113] The terms "aging parameter", "aging parameter category", and "aging parameter factor" have been specified above. As will be understood by those skilled in the art from this specification, the assignment of aging parameter factor values to aging parameter category values is hampered by the fact that, in each chromatographic separation, a set of aging parameter category values is applied to the chromatographic column. Thus, in order to determine the contribution of a single aging parameter category, the effect of two sets of aging factor categories on the column performance is compared, where only the target aging parameter category has changed. Thus, in one embodiment, the second set of aging parameter category values differs from the first set of aging parameter category values by one aging parameter category value. However, there may also be cases where the effect of the change of multiple aging parameter categories is of interest, for example if the sample is switched from a low-volume serum sample to a high-volume urine sample; in such cases, in one embodiment, the second set of aging parameter category values differs from the first set of aging parameter category values by multiple aging parameter category values.

[0114] In one embodiment, the method optionally further comprises the additional step (VII) of comparing the difference between a third value and a second value of a performance parameter with the difference between the second value and a first value of the performance parameter, and based on said comparison, determining the value of one or more aging parameter factors that differ between the first and second sets of aging parameter values.

[0115] The term "data set" refers to a collection of data that can be physically and / or logically grouped together. Thus, a data set can be implemented in a single storage medium or in physically separate storage media that are operatively connected to each other. In one embodiment, a data set is implemented by a database. Thus, as used herein, a database includes a data set on a suitable storage medium. Additionally, in one embodiment, the database further includes a database management system. In one embodiment, the database management system is a web-based, hierarchical, or object-oriented database management system. Additionally, the database can be a federated or integrated database. In another embodiment, the database will be implemented as a distributed (federated) system, such as implemented as a client-server system. In another embodiment, the database is constructed to allow a search algorithm to compare a test data set with the data sets included in the data set. Specifically, by using such an algorithm, data sets in the database that indicate a medical condition or effect can be searched for that are similar or identical, as described above (e.g., query search). Thus, if an identical or similar data set can be identified in the data set, the test data set is associated with the medical condition or effect. Thus, the information obtained from the data set can be used as a reference for, for example, the method of the present invention described above.

[0116] As used herein, the term "storage medium" includes data storage media based on a single physical entity, such as CDs, CD-ROMs, hard drives, optical storage media, or floppy disks. Additionally, the term further includes data storage media composed of physically separate entities that are operably connected to each other in a manner that provides the above data set, and in one embodiment, are connected to each other in a manner suitable for query search.

[0117] The invention also relates to a data set that is tangibly embedded on a storage medium in one embodiment. The data set includes at least one general weighted aging factor determined according to a method for determining a general weighted aging factor and / or includes at least a set of aging parameter factor values annotated to aging parameter category values and optionally annotated to a chromatographic scheme, where the aging parameter category values include at least one category value of aging parameters selected from sample type, sample dilution, and sample volume, and in one embodiment, the values are obtained according to the method for establishing a data set of annotated aging parameter categories and aging parameter factors described herein.

[0118] In view of the above, in one embodiment, the data set further includes at least one of the following, at least two in one embodiment, at least three in another embodiment, and all in another embodiment: (i) a parameter indicating the initial performance of the chromatographic column; (ii) a parameter indicating the performance requirements of the target determination; (iii) a parameter indicating the current performance of the chromatographic column; and (iv) a parameter indicating column load aging. Additionally, the database may further include one or more reference values.

[0119] The invention also relates to an apparatus for determining a second service life value of a chromatographic column, which includes

[0120] (a) a storage medium that includes a tangibly embedded data set, the data set including at least a set of aging parameter factor values annotated to aging parameter category values and optionally annotated to a chromatographic scheme, where the aging parameter category values include at least one category value of aging parameters selected from sample type, sample dilution, and sample volume; and a data set tangibly embedded on the storage medium, the data set including the first service life value of the chromatographic column and / or the initial service life value of the chromatographic column,

[0121] (b) an input unit configured to receive input data indicating at least one aging parameter factor value; and

[0122] (c) a data processing unit, where the data processing unit is configured to calculate the second service life value of the chromatographic column based on the input data indicating at least one aging parameter factor value, the first service life value of the chromatographic column, and / or the initial service life value.

[0123] As used herein, the term "device" refers to a collection of tools that are operably connected to each other to provide the indicated function. The device can be implemented in a single physical unit or in physically separate units that are operably connected to each other. Suitable components and their properties are described elsewhere herein and also above in the context of the method. Thus, one or more methods of the present invention can be implemented by the devices specified herein. Thus, in one embodiment, the device is configured to perform at least one method as specified elsewhere herein. The device can include additional units, particularly an output unit, a communication interface, and / or any other unit that a person skilled in the art deems appropriate.

[0124] As used herein, the term "input unit" refers to any unit that is configured to transfer information from another entity to the device (particularly its data processing unit or data storage medium), where the other entity can be another data processing device or a user. Thus, the input unit can include a user interface; however, the input unit can also be a storage medium that includes a data set from which appropriate values can be retrieved. However, the input unit can also be an interface to an analysis unit that measures at least one input data indicating an aging parameter factor value.

[0125] The term "input data indicating at least one aging parameter factor value" includes all data from which an aging parameter factor value can be derived (e.g., by calculation or retrieval from a data set). Thus, the input data indicating at least one aging parameter factor value can particularly be a value of a performance parameter, a value of an aging parameter category, and / or the aging parameter factor itself, and in one embodiment, a value of an aging parameter category.

[0126] The term "data processing unit" generally refers to any unit that is suitable for performing one or more of the method steps described above, and in one embodiment, is performed by using at least one processor and / or at least one application-specific integrated circuit. Thus, by way of example, the at least one data processing unit can include software code stored thereon that includes a plurality of computer instructions. The data processing unit can provide one or more hardware elements for performing one or more of the indicated operations, and / or can provide software for running on one or more processors for performing one or more method steps.

[0127] As used herein, the term "output unit" refers to any unit that is configured to transfer information from the system to another entity, where the other entity can be another data processing device and / or a user. Thus, the output device can include a user interface (such as a suitably configured display), or can be a printer. However, the output unit can also be an indicator, such as an indicator light, that indicates that a second service life value exceeds a predetermined reference value.

[0128] The term "communication interface" is understood by those skilled in the art to refer to any interface configured for information exchange, particularly data exchange. Such data exchange can be achieved through permanent or temporary physical connections, such as coaxial cables, fiber optic cables, optical fibers or twisted pair cables, 10BASE-T cables, storage unit connectors (such as USB, FireWire and similar connectors). Alternatively, it can be achieved through temporary or permanent wireless connections using, for example, radio waves such as Wi-Fi, LTE, LTE Advanced or Bluetooth, etc.

[0129] The present invention also relates to a system comprising a chromatographic column and the device of the present invention.

[0130] Furthermore, the present invention relates to the use of a weighted aging factor for determining the service life of a chromatographic column.

[0131] The present invention further discloses and provides a computer program comprising computer-executable instructions for performing the method according to the present invention in one or more of the embodiments appended hereto when the program is executed on a computer or a computer network. Specifically, the computer program can be stored on a computer-readable data carrier. Thus, specifically, one, more than one or even all of the method steps as indicated above can be performed by using a computer or a computer network, preferably by using the computer program.

[0132] The present invention further discloses and provides a computer program product having program code means for performing the method according to the present invention in one or more of the embodiments appended hereto when the program is executed on a computer or a computer network. Specifically, the program code means can be stored on a computer-readable data carrier.

[0133] Furthermore, the present invention discloses and provides a data carrier having a data structure stored thereon, which can perform the method according to one or more of the embodiments disclosed herein after being loaded into a computer or a computer network, such as after being loaded into the working memory or main memory of a computer or a computer network.

[0134] The present invention further provides and discloses a computer program product having program code means stored on a machine-readable carrier for performing the method according to one or more of the embodiments disclosed herein when the program is executed on a computer or a computer network. As used herein, a computer program product refers to a program as a tradable product. The product can generally exist in any format (such as in paper format), or on a computer-readable data carrier. Specifically, the computer program product can be distributed over a data network.

[0135] Finally, the present invention provides and discloses a modulated data signal comprising instructions readable by a computer system or a computer network for performing a method according to one or more embodiments disclosed herein.

[0136] In one embodiment, with reference to the computer-implemented aspects of the present invention, one or more method steps or even all method steps of a method according to one or more embodiments disclosed herein can be performed by using a computer or a computer network. Thus, generally speaking, any method step including providing and / or processing data can be performed by using a computer or a computer network. Generally speaking, these method steps can include any method steps other than those that generally require manual operations (such as providing samples and / or performing certain aspects of actual measurements).

[0137] Specifically, the present invention further discloses:

[0138] A computer or a computer network comprising at least one processor, wherein the processor is adapted to perform a method according to one of the embodiments described in this specification,

[0139] A computer-loadable data structure adapted to perform a method according to one of the embodiments described in this specification when the data structure is executed on a computer,

[0140] A computer program, wherein the computer program is adapted to perform a method according to one of the embodiments described in this specification when the program is executed on a computer,

[0141] A computer program comprising program tools for performing a method according to one of the embodiments described in this specification when the computer program is executed on a computer or on a computer network,

[0142] A computer program comprising program tools according to the foregoing embodiments, wherein the program tools are stored on a computer-readable storage medium,

[0143] A storage medium on which a data structure is stored and wherein the data structure is adapted to perform a method according to one of the embodiments described in this specification after being loaded into the main memory and / or working memory of a computer or a computer network, and

[0144] A computer program product having program code tools, wherein the program code tools can be stored or are stored on a storage medium for performing a method according to one of the embodiments described in this specification when the program code tools are executed on a computer or a computer network.

[0145] In summary, the following embodiments are particularly contemplated:

[0146] 1. A method for operating a chromatographic column, comprising

[0147] (a) providing a first value of the service life of the chromatographic column (first service life value);

[0148] (b) performing chromatographic separation of a sample on the chromatographic column;

[0149] (c) providing a value of a weighted aging factor determined based on at least one aging parameter selected from sample type, sample dilution, and sample volume; and

[0150] (d) determining a second value of the service life of the chromatographic column (second service life value) based on the first service life value and the weighted aging factor.

[0151] 2. The method according to embodiment 1, wherein the sample type is defined by the sample matrix and / or the pre-purification state of the sample.

[0152] 3. The method according to embodiment 1 or 2, wherein the value of the weighted aging factor is calculated based on at least one additional aging parameter selected from the time since the previous use, the storage conditions since the previous use, and the set of chromatographic conditions applied.

[0153] 4. The method according to any one of embodiments 1 to 3, wherein the value of the weighted aging factor is calculated based on aging parameters including sample type, sample dilution, and sample volume.

[0154] 5. The method according to any one of embodiments 1 to 4, wherein the value of the weighted aging factor is calculated based on aging parameters including sample type, sample dilution, sample volume, and the set of chromatographic conditions applied.

[0155] 6. The method according to any one of embodiments 1 to 5, wherein the aging parameters are combined into a single, assay-specific weighted aging factor.

[0156] 7. The method according to any one of embodiments 1 to 6, wherein the method further comprises a step (e) of comparing the second service life value with a reference value.

[0157] 8. The method according to embodiment 7, wherein the use of the chromatographic column is stopped or modified based on the result of the comparison step (e).

[0158] 9 The method according to embodiment 8, wherein if the second service life value is outside a predefined reference range or exceeds a reference threshold, the use of the chromatographic column is stopped or modified.

[0159] 10. The method according to embodiment 8 or 9, wherein said modified use comprises reloading the chromatography column and / or retaining the chromatography column for applications where lower performance is required.

[0160] 11. The method according to any one of embodiments 1 to 10, wherein said weighted aging factor is calculated according to equation (1):

[0161] F = T × D × V (1)

[0162] where F = weighted aging factor;

[0163] T = sample type aging parameter;

[0164] D = sample dilution aging parameter; and

[0165] V = sample volume aging parameter.

[0166] 12. The method according to any one of embodiments 1 to 11, wherein said second service life value is calculated according to equation (3):

[0167] R L = R L-1 - F (3)

[0168] where R L = second service life value;

[0169] R L-1 = first service life value; and

[0170] F = weighted aging factor, preferably calculated according to embodiment 11.

[0171] 13. The method according to any one of embodiments 1 to 11, wherein said second service life value is calculated according to equation (4):

[0172] R L = R L-1 + F (4)

[0173] where R L = second service life value;

[0174] R L-1 = first service life value; and

[0175] F = weighted aging factor, preferably calculated according to embodiment 11.

[0176] 14. The method according to any one of embodiments 1 to 13, wherein said first service life value of said column is provided based on an initial value of the service life of said chromatography column (initial service life value) and any weighted aging factors from previous use.

[0177] 15. The method according to embodiment 14, wherein the initial service life value is a value specific to the column type.

[0178] 16. The method according to any one of embodiments 1 to 15, wherein determining the second service life value in step b) is further based on at least one of the following:

[0179] (i) A parameter indicating the initial performance of the column, which is determined during factory testing in one embodiment;

[0180] (ii) A parameter indicating the performance requirements of the assay used;

[0181] (iii) A parameter indicating the current performance of the column; and

[0182] (iv) A parameter indicating column loading aging, which is the time and / or temperature held by the column in one embodiment.

[0183] 17. The method according to embodiment 16, wherein the parameters indicating performance in (i) and / or (iii) are selected from retention time, peak width, peak symmetry, resolution, breakthrough point, and column pressure.

[0184] 18. The method according to any one of embodiments 1 to 17, wherein multiple chromatographic separations are performed on the column, wherein the first service life value is the initial service life value, and wherein the second service life value is according to equation (6)

[0185]

[0186] where R L = second service life value;

[0187] R0 = initial service life value

[0188] T i = sample type aging parameter for chromatographic separation i;

[0189] D i = sample dilution aging parameter for chromatographic separation i;

[0190] V i = sample volume aging parameter for chromatographic separation i; and

[0191] n = total number of chromatographic separations performed on the column.

[0192] 19. The method according to any one of embodiments 1 to 19, wherein multiple chromatographic separations are performed on the column, and wherein the second service life value is the used service life value calculated according to equation (8)

[0193]

[0194] where R L = second service life value;

[0195] R0 = initial service life value

[0196] T i = sample type aging parameter for chromatographic separation i;

[0197] D i = sample dilution aging parameter for chromatographic separation i;

[0198] V i = sample volume aging parameter for chromatographic separation i; and

[0199] n = total number of chromatographic separations performed on the chromatographic column.

[0200] 20. The method according to any one of embodiments 1 to 19, wherein the second service life value is the current service life value.

[0201] 21. A method for establishing a data set of annotated aging parameter categories and aging parameter factors for a chromatographic column, the data set being preferably tangibly embedded on a storage medium, the method comprising

[0202] (I) determining at least one first value of a performance parameter of the chromatographic column;

[0203] (II) performing at least one chromatographic separation, and in one embodiment multiple chromatographic separations, under conditions of a first set of aging parameter category values;

[0204] (III) determining at least one second value of the performance parameter;

[0205] (IV) performing at least one chromatographic separation, and in one embodiment multiple chromatographic separations, under conditions of a second set of aging parameter category values; wherein the second set of aging parameter category values is different from the first set of aging parameter category values;

[0206] (V) determining at least one third value of the performance parameter; and

[0207] (VI) determining values of aging parameter factors for at least one aging parameter category based on the first performance parameter, the second performance parameter, and the third performance parameter or values derived therefrom; and the first set of aging parameter category values and the second set of aging parameter category values or values derived therefrom, and annotating the values of the at least one aging parameter category and the values of the aging parameter factors to the data set.

[0208] 22. The method according to embodiment 21, wherein the second set of aging parameter category values differs from the first set of aging parameter category values by one aging parameter category value.

[0209] 23. The method according to embodiment 21 or 22, wherein the method further comprises an additional step (VII) of comparing the difference between a third value and a second value of a performance parameter with the difference between the second value and a first value of the performance parameter, and based on the comparison, determining the value of one or more aging parameter factors that differ between the first set and the second set of aging parameter values.

[0210] 24. A data set, tangibly embedded in a storage medium in one embodiment, the data set comprising at least one set of aging parameter factor values annotated to aging parameter category values and optionally annotated to a chromatographic scheme, wherein the aging parameter category values comprise at least one category value of an aging parameter selected from sample type, sample dilution, and sample volume and / or comprise at least one general weighted aging factor determined according to the method of embodiment 32.

[0211] 25. A device for determining a second service life value of a chromatographic column, comprising

[0212] (a) A storage medium comprising a data set tangibly embedded therein, the data set comprising at least one set of aging parameter factor values annotated to aging parameter category values and optionally annotated to a chromatographic scheme, wherein the aging parameter category values comprise at least one category value of an aging parameter selected from sample type, sample dilution, and sample volume; and a data set tangibly embedded in the storage medium, the data set comprising the first service life value of the chromatographic column and / or the initial service life value of the chromatographic column,

[0213] (b) An input unit configured to receive input data indicative of at least one aging parameter factor value; and

[0214] (c) A data processing unit, wherein the data processing unit is configured to calculate the second service life value of the chromatographic column based on the input data indicative of at least one aging parameter factor value, the first service life value of the chromatographic column, and / or the initial service life value.

[0215] 26. A system comprising a chromatographic column and the device according to embodiment 25.

[0216] 27. Use of a weighted aging factor for determining the service life of a chromatographic column.

[0217] 28. A method for operating a chromatographic column, comprising

[0218] (a) Provide an initial value (initial service life value) of the service life of the chromatographic column;

[0219] (b) Perform chromatographic separation of a sample on the chromatographic column;

[0220] (c) Provide a parameter value indicating the initial performance of the chromatographic column based on the chromatographic separation in step (b); and

[0221] (d) Determine a corrected initial value (corrected initial service life value) of the initial service life of the chromatographic column based on the initial service life value and the parameter indicating the initial performance of the chromatographic column.

[0222] 29. The present invention also relates to a method for operating a chromatographic column, the method comprising

[0223] (a) Provide a first value (first service life value) of the service life of the chromatographic column;

[0224] (b) Provide a parameter value indicating the performance requirements of a target determination; and

[0225] (c) Determine a second value (second service life value) of the service life of the chromatographic column based on the first service life value and the value of the parameter indicating the performance requirements of the target determination.

[0226] 30. The present invention also relates to a method for operating a chromatographic column, the method comprising

[0227] (a) Provide a first value (first service life value) of the service life of the chromatographic column;

[0228] (b) Perform chromatographic separation of a sample on the chromatographic column;

[0229] (c) Provide a parameter value indicating the current performance of the chromatographic column based on the chromatographic separation in step (b); and

[0230] (d) Determine a second value (second service life value) of the service life of the chromatographic column based on the first service life value and the value of the parameter indicating the current performance of the chromatographic column.

[0231] 31. The present invention also relates to a method for operating a chromatographic column, the method comprising

[0232] (a) Provide a first value (first service life value) of the service life of the chromatographic column;

[0233] (b) Provide a parameter value indicating column carrier aging; and

[0234] (c) Determine a second value (second service life value) of the service life of the chromatographic column based on the first service life value and the value of the parameter indicating column loading aging.

[0235] 32. A method for determining a general weighted aging factor for chromatographic determination, comprising the following steps

[0236] (I) Determine at least one first value of the performance parameters of the chromatographic column;

[0237] (II) Perform at least one, preferably multiple, chromatographic separations under the determination conditions;

[0238] (III) Determine at least one second value of the performance parameters; and

[0239] (IV) Determine the value of the general weighted aging parameter factor for the chromatographic determination based on the first and second performance parameters or values derived therefrom.

[0240] 33. The subject matter according to any one of embodiments 21 to 32 further includes the subject matter according to any one of embodiments 1 to 20.

[0241] 34. The method according to any one of embodiments 1 to 20, wherein step (c) is to provide a value of a weighted aging factor, and the value of the weighted aging factor is determined based on at least one sample-specific aging parameter selected from sample type, sample dilution, and sample volume and based on at least one operation-specific aging parameter.

[0242] 35. The method according to embodiment 34, wherein the operation-specific aging parameter is a determination-specific parameter, the time since the previous use, the storage conditions since the previous use, and / or a parameter indicating solvent replacement.

[0243] 36. The method according to embodiment 35, wherein the determination-specific aging parameter is the eluent pH and / or the pressure conditions.

[0244] 37. The method according to embodiment 36, wherein the weighted aging factor (F) for one separation is calculated according to equation (10):

[0245] F = T × D × V × E × P × S (10)

[0246] where T = sample type aging parameter; D = sample dilution aging parameter; V = sample volume aging parameter; E = eluent pH aging parameter; P = pressure condition aging parameter; S = solvent replacement aging parameter.

[0247] 38. The method according to embodiment 36, wherein multiple chromatographic separations are performed on the chromatographic column, and wherein the weighted aging factor (F) is calculated according to equation (11):

[0248]

[0249] wherein Ti = sample type aging parameter for chromatographic separation i; Di = sample dilution aging parameter for chromatographic separation i; Vi = sample volume aging parameter for chromatographic separation i; Ei = eluent pH aging parameter for chromatographic separation i; Pi = pressure condition aging parameter for chromatographic separation i; Si = solvent change aging parameter for chromatographic separation i, and n = total number of chromatographic separations performed on the chromatographic column.

[0250] The entire disclosure of all references cited in this specification and the disclosures specifically mentioned in this specification are incorporated herein by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0251] Figure 1 : Schematic diagram of an exemplary method of the present invention.

[0252] Figure 2 : Factors affecting the service life of the chromatographic column; α: measurement adjustment factor specific to the determination (sample amount, sample type, sample preparation, LC elution); β: column load aging adjustment; δ: continuous prediction of column service life; γ: initial prediction of column service life.

[0253] Figure 3 : Example graph of the remaining service life value changing with the number of injections and the regression line for predicting the end time of column availability.

[0254] The following examples are intended to illustrate the invention only. In no way should they be construed as limiting the scope of the invention.

[0255] Example 1

[0256] To overcome the disadvantages of the prior art, particularly the disadvantages of a simple service life counter, the present invention proposes the use of a weighted counter (optionally with several additional adjustment factors). This weighted counter takes into account the pressure exerted on the chromatographic column by the sample of each individual injection. The individual factors for different column aging effects can be stored in a database and / or determined continuously.

[0257] Factors such as matrix type, sample preparation, sample dilution, and injection volume can be combined into a single factor for each assay, for example, as an assay weighting factor. Then, the column service life after each injection is adjusted using the assay-specific weighting factor. Since different assays can tolerate different column aging stages, each assay may have its own individual measurement limit. These two factors define the column service life for each assay, and the procedure supports performing multiple assays on one column type.

[0258] Both of the above factors can be determined experimentally and stored in a database. In a multi-column setup (LC multiplexing), one column can be used for less demanding assays, while the column has reached its service life for more demanding assays and the assay is measured on a new column.

[0259] To account for the uniqueness of each column, an adjustment factor (e.g., determined by factory testing) that affects the maximum number of available measurements can be additionally used. Additionally, monitoring of chromatographic parameters such as retention time or resolution can be used for the column usage factor, which continuously adjusts the maximum injection count based on the current column performance. This factor corrects for the influence of individual samples. Both of these factors can be determined by measurements performed on a specific column. The adjustment factor for column uniqueness can be determined before column shipment and added to the database together with the individual column characteristics, or it can be determined directly after column installation and then written to the database. The adjustment factor for individual column usage can be determined continuously during column use, and this factor directly adjusts the weighting counter.

[0260] The column loading time can also affect the column service life. Therefore, a factor for column loading aging (e.g., exposure to high temperature) can be applied to the service life calculation. This factor can be determined experimentally and stored in the database.

[0261] The above factors, either alone or in combination, can be used to improve the assay-dependent use of the column. In a multi-column system, the instrument can switch a demanding assay to a new column at the end of the column service life. During use, the user can be informed about the column health and remaining column service life via a display (e.g., a column service life bar).

[0262] Buy Example 2

[0263] In an experiment, columns of the same type were used for different assays. The first column was subjected to injections of undiluted matrix samples, representing an assay requiring high sensitivity. After 700 injections, the column was no longer usable.

[0264] For comparison, the matrix was diluted and injected into another column from the same batch as the first column using the same sampling method. This represents an assay where the analyte is present at a high concentration in the patient sample and thus the sample may be diluted prior to the assay. Using the diluted matrix sample, the column life was 2300 injections.

[0265] In summary, when injecting with the undiluted matrix, a weighting factor 3.29 times higher must be used compared to injecting with the diluted matrix sample.

[0266] Example 3:

[0267] Reference Figure 1 shows an exemplary embodiment of the method of the present invention. Ten after the start of the method, a first service life value 20 is provided and chromatographic separation 30 is performed. Based on at least one aging parameter selected from sample type, sample dilution, and sample volume, the value of the weighted aging factor is determined 40. The weighted aging factor can be calculated, for example, based on aging parameter factors that can be retrieved from a data set 50. It should be understood that the information required for the retrieval can be input by the user or can be provided, for example, by selecting the assay to be performed. Based on the weighted aging factor, a second service life value 60 is calculated, which can be compared with a reference value 70. Depending on the result of the comparison, column use can be ended 80, or further use can continue, where the second service life value of step 60 can be used as the first service life value in step 20 for the next separation.

[0268] Example 4:

[0269] Reference Figure 2 In the embodiment as specified above, several factors may affect the chromatographic column service life. Based on these factors, the service life can be calculated according to Equation (10):

[0270] R ij+1 = R m0 ×γ i ×δ ij -1×α k -β m ×(t ij -t ij -1) (10),

[0271] where

[0272]

[0273] Example 5:

[0274] A table showing example values of aging parameters, weighted aging factors, and remaining service life values is shown in Table 1. Figure 3Shows an exemplary use of the method of the present invention in predicting the end time of column availability.

[0275]

[0276] Reference signs

[0277] 10 Start

[0278] 20 Provide a first service life value

[0279] 30 Chromatographic separation

[0280] 40 Provide the value of a weighted aging factor

[0281] 50 Data set

[0282] 60 Determine a second service life value

[0283] 70 Has the second service life value exceeded the reference value? (y: yes, n: no)

[0284] 80 End of column service life

[0285] Document:

[0286] -EP 2 771 683 A1

[0287] -EP 2 338 049 A1

[0288] -EP 2 880 437 A1

[0289] -US 8,279,072 B2

Claims

1. A method for operating a chromatographic column, which comprises (a) providing a first value of the service life of the chromatographic column, namely the first service life value; (b) performing chromatographic separation of a sample on the chromatographic column; (c) providing a value of a weighted aging factor determined based on at least one aging parameter selected from sample type, sample dilution, and sample volume; and (d) determining a second value of the service life of the chromatographic column, namely the second service life value, based on the first service life value and the weighted aging factor.

2. The method according to claim 1, wherein the sample type is defined by the sample matrix and / or the pre-purification state of the sample.

3. The method according to claim 1 or 2, wherein the value of the weighted aging factor is calculated based on at least one additional aging parameter selected from the time since the previous use, the storage conditions since the previous use, and the set of chromatographic conditions applied.

4. The method according to claim 1 or 2, wherein the method further comprises a step (e) of comparing the second service life value with a reference value.

5. The method according to claim 4, wherein based on the result of step (e), the use of the chromatographic column is stopped or modified, and the modified use includes re-packing the chromatographic column and / or retaining the chromatographic column for applications where lower performance is required.

6. The method according to claim 1 or 2, wherein the weighted aging factor is calculated according to equation (1): F = T × D × V (1) where F = weighted aging factor; T = sample type aging parameter; D = sample dilution aging parameter; and V = sample volume aging parameter.

7. The method according to claim 6, wherein the second service life value is calculated according to equation (3): R L = R L-1 - F(3); or calculated according to equation (4): R L = R L-1 + F(4) where R L = second service life value; R L-1 = first service life value; and F = weighted aging factor, calculated according to claim 6.

8. The method according to claim 1 or 2, wherein providing the first service life value of the column is based on the initial value of the service life of the chromatographic column, namely the initial service life value, and the weighted aging factor of any previous use.

9. The method according to claim 1 or 2, wherein determining the second service life value in step (d) is further based on at least one of the following: (i) a parameter indicating the initial performance of the chromatographic column, which is determined during the factory test; (ii) a parameter indicating the performance requirements of the determination used; (iii) a parameter indicating the current performance of the chromatographic column; and (iv) a parameter indicating column loading aging, which includes the time and / or temperature held by the column.

10. The method according to claim 1 or 2, wherein multiple chromatographic separations are performed on the chromatographic column, wherein the first service life value is the initial service life value, and wherein the second service life value is the remaining service life value calculated according to equation (6) or calculated according to equation (8) where where R L = second service life value; R0 = initial service life value T i = Aging parameter of the sample type for chromatographic separation i; D i = Sample dilution aging parameter for chromatographic separation i; V i = sample volume aging parameter for chromatographic separation i; and n = total number of chromatographic separations performed on the chromatographic column.

11. The method according to claim 1 or 2, wherein step (c) is to provide a value of a weighted aging factor, and the value of the weighted aging factor is determined based on at least one sample-specific aging parameter selected from sample type, sample dilution, and sample volume, and based on at least one operation-specific aging parameter.

12. The method according to claim 11, wherein the operation-specific aging parameter is a determination-specific parameter, the time since the previous use, the storage conditions since the previous use, and / or a parameter indicating a solvent change.

13. The method according to claim 12, wherein the determination-specific aging parameter is the eluent pH and / or the pressure conditions.

14. A method for establishing a data set of annotated aging parameter categories and aging parameter factors for a chromatographic column, the method comprising (I) determining at least one first value of a performance parameter of the chromatographic column; (II) performing at least one chromatographic separation under a first set of aging parameter category values; (III) determining at least one second value of the performance parameter; (IV) performing at least one chromatographic separation under a second set of aging parameter category values, wherein the second set of aging parameter category values is different from the first set of aging parameter category values; (V) determining at least one third value of the performance parameter; and (VI) based on the first value, the second value, and the third value or values derived therefrom; and the first set of aging parameter category values and the second set of aging parameter category values or values derived therefrom, determining the value of the aging parameter factor for at least one aging parameter category, and annotating the value of the at least one aging parameter category and the value of the aging parameter factor into the data set, wherein the aging parameter category values include at least one category value of aging parameters selected from sample type, sample dilution, and sample volume.

15. A data set comprising at least one set of aging parameter factor values annotated to aging parameter category values, wherein the aging parameter category values include at least one category value of aging parameters selected from sample type, sample dilution, and sample volume, and wherein the aging parameter factor values are obtained by the method according to claim 14.

16. A device for determining a second service life value of a chromatographic column, comprising (a) A storage medium, which includes a tangibly embedded data set, the data set including at least a set of aging parameter factor values annotated to aging parameter category values, wherein the aging parameter category values include at least one category value of aging parameters selected from sample type, sample dilution, and sample volume; and a data set tangibly embedded on a storage medium, the data set comprising the first service life value and / or the initial service life value of the chromatographic column, (b) an input unit configured to receive input data indicating at least one aging parameter factor value; and (c) a data processing unit, wherein the data processing unit is configured to calculate the second service life value of the chromatographic column based on the input data indicating at least one aging parameter factor value, the first service life value and / or the initial service life value of the chromatographic column.

17. A computer program product having instructions that, when executed by a computer, cause the computer to execute the method according to any one of claims 1-14.

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