Stabilizing oxygen in compositions

Abstract

Example compositions include one or more analytes for use with an electrochemical sensor configured to detect a component of a biological sample, and a quinolone-based compound at a concentration of 60 mg / L (mg / L) to 120 mg / L in the composition, and the quinolone-based compound is used to stabilize oxygen in the presence of a trace metal.

Description

Technical Field

[0001] This specification generally relates to diagnostic tests and the devices, test kits, containers, and boxes used during diagnostic tests. Background Art

[0002] Molecular oxygen or dioxygen is an active component in multi - analyte solutions commonly used in test systems such as blood gas analyzers. Oxidation reactions are processes in which a chemical substance formally loses electrons and can be mediated directly or indirectly by molecular oxygen with or without the incorporation of some form of oxygen into the chemical substance. For example, the oxidation (auto - oxidation) of organic compounds or biomolecules can be catalyzed by certain metal ions, and certain metal ions can be directly oxidized by molecular oxygen. When a substance such as a metal is oxidized, the result is that the amount of molecular oxygen in the composition is less than the amount before oxidation occurred. Summary of the Invention

[0003] This specification generally relates to stabilizing molecular oxygen in a composition by incorporating a chelating agent such as a quinolone compound into the composition.

[0004] Example compositions include one or more analytes for use with an electrochemical sensor and a quinolone compound at a concentration of 60 milligrams per liter (mg / L) to 120 mg / L in the composition, wherein the electrochemical sensor is configured to detect the components of a biological sample, and the quinolone compound is used to stabilize oxygen in the presence of trace metals. Example compositions may include one or more of the following features.

[0005] The quinolone compound can be or include a fluoroquinolone compound. The quinolone compound can be or include levofloxacin. The quinolone compound can be or include at least one of the following: ciprofloxacin, gemifloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, enoxacin, amifloxacin, tosufloxacin, difloxacin, temafloxacin, miloxacin, cinoxacin, lomefloxacin, fleroxacin, fluoroquinolones, nalidixic acid, pipemidic acid, piromidic acid, rosoxacin, oxolinic acid, flumequine, enrofloxacin, sparfloxacin, gatifloxacin, balofloxacin, clinafloxacin, or sitafloxacin.

[0006] The composition can comprise an aqueous liquid. The trace metals in the composition can include one or more metals. The concentration of the one or more metals in the composition can be ten parts per billion (10 ppb) or higher. The aqueous liquid can contain dissolved oxygen. The one or more analytes can include: pH (hydronium ion), carbon dioxide (CO 2 ), oxygen (O 2 ), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), magnesium (Mg), glucose, lactate, creatinine, urea, organic dyes, amaranth, or sulforhodamine B. The concentration of the dissolved oxygen in the composition can be known.

[0007] The container can hold a composition that includes one or more analytes for use with an electrochemical sensor and a quinolone compound at a concentration in the composition of 60 milligrams per liter (mg / L) to 120 mg / L. The electrochemical sensor is configured to detect components of a biological sample. The quinolone compound is used to stabilize oxygen in the presence of trace metals. The container can be or include a bag, a pouch, or glass. The container can be or include a box.

[0008] An example system includes a box having a plurality of containers. Each of the plurality of containers holds a composition. Each composition includes: a liquid that includes one or more analytes, and a quinolone compound at a concentration in the composition of 60 milligrams per liter (mg / L) to 120 mg / L. The liquids in different containers have different concentrations of one or more analytes. The example system also includes an electrochemical sensor configured to detect at least one analyte. The electrochemical sensor can be located inside or outside the box. The example system can include one or more of the following features, alone or in combination.

[0009] The quinolone compound can be or include levofloxacin. The quinolone compound can be or include at least one of the following drugs: ciprofloxacin, gemifloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, enoxacin, amifloxacin, tosufloxacin, difloxacin, temafloxacin, miloxacin, cinoxacin, lomefloxacin, fleroxacin, fluoroquinolones, nalidixic acid, pipemidic acid, piromidic acid, rosoxacin, oxolinic acid, flumequine, enrofloxacin, sparfloxacin, gatifloxacin, balofloxacin, clinafloxacin, or sitafloxacin.

[0010] The composition may comprise one or more metals. The concentration of the one or more metals in the corresponding composition may be ten parts per billion (10 ppb) or higher. The composition may comprise an aqueous liquid. The aqueous liquid may contain dissolved oxygen. The dissolved oxygen may be one of the analytes. The one or more analytes may include: pH (hydronium ion), carbon dioxide (CO 2 ), oxygen (O 2 ), sodium (Na), potassium (K), chloride (Cl), calcium (Ca), magnesium (Mg), glucose, lactate, an organic dye, sulforhodamine B, or amaranth.

[0011] An exemplary kit comprises a quinolone compound and an aqueous composition comprising one or more analytes for use with an electrochemical sensor configured to detect a biological sample component.

[0012] An exemplary method performs oxygen measurement in a composition comprising one or more analytes for use with an electrochemical sensor configured to detect a biological sample component and a quinolone compound at a concentration of 60 milligrams per liter (mg / L) to 120 mg / L in the composition, the quinolone compound being for stabilizing oxygen in the presence of trace metals. The exemplary method includes contacting the surface of an inert metal electrode with the composition, reducing oxygen at the surface, and generating an electrical signal that is detected by a clinical analyzer. The quinolone compound stabilizes oxygen in the composition prior to oxygen measurement. The exemplary method may include one or more of the following features alone or in combination.

[0013] The quinolone compound may optionally be or include levofloxacin. The quinolone compound may optionally be or include at least one of the following drugs: ciprofloxacin, gemifloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, enoxacin, amifloxacin, tosufloxacin, difloxacin, temafloxacin, miloxacin, cinoxacin, lomefloxacin, fleroxacin, fluoroquinolones, nalidixic acid, pipemidic acid, piromidic acid, rosoxacin, oxolinic acid, flumequine, enrofloxacin, sparfloxacin, gatifloxacin, balofloxacin, clinafloxacin, or sitafloxacin. Optionally, the composition may be contained in a sealed container prior to oxygen measurement. Optionally, the composition may contain one or more metals, the concentration of which is optionally 10 parts per billion (10 ppb) or more.

[0014] The compositions, devices, systems, and processes described in this specification may be configured, for example, by design, configuration, formulation, arrangement, placement, programming, operation, activation, deactivation, and / or control.

[0015] Two or more features described in this specification (including the Summary of the Invention section) may be combined to form implementations not specifically described in this specification.

[0016] Details of one or more embodiments will be set forth in the following drawings and description. Other features and advantages will be apparent from the specification and drawings, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 is a block diagram of an exemplary container containing an exemplary composition that contains metal contaminants and a chelating agent.

[0018] Figure 2 is a block diagram conceptually illustrating an exemplary chelation process.

[0019] Figure 3 is a block diagram of components of an exemplary test system that includes an exemplary composition containing a chelating agent.

[0020] Like reference numerals indicate like elements. DETAILED DESCRIPTION

[0021] The exemplary test system uses a liquid composition that contains an aqueous liquid such as deionized (DI) water or a buffer solution described herein and a known, predetermined concentration of dissolved oxygen. The composition can be stored in a sealed, substantially airtight container such as a bag, sachet, or glass bottle. The dissolved oxygen can be one of the analytes to be detected by an electrochemical sensor (hereinafter simply referred to as "sensor") in the test system. "Oxygen" as used herein refers to molecular oxygen, dioxygen, or free oxygen in this context, including oxygen atoms not attached to other elements.

[0022] The composition can be part of a calibration solution or a control solution. For example, the test system can use the composition to calibrate the sensor. In one example, the test system can detect the oxygen concentration in the composition and compare the detected oxygen concentration with the known oxygen concentration in the composition. If the two concentrations are different, the test system can apply a calibration factor to the measured value of the sensor.

[0023] The composition also contains trace metals, including metal ions. These trace metal ions are contaminants that may be inadvertently introduced by production equipment during the manufacture of the container or the composition, or are contaminants in the raw materials used to formulate the composition. To prevent, limit, or minimize the oxidation of metal ions, a chelating agent such as a quinolone compound is added to the composition in the container.

[0024] The chelating agent forms stable complexes with these metal ions through two or more covalent or coordination bonds, thereby binding to the contaminant metal ions. Its main function is to render the metal ions inert to oxygen, thereby preventing or limiting the oxidation reaction in the composition and the consequent oxygen consumption. Generally, in some embodiments, the chelating agent does not react with any components of the composition other than the metal contaminants. For example, the chelating agent may not chemically react with any detectable or measurable amount of analyte, test sample, or active components of the sensor (such as the reagents included on the sensor) in the composition.

[0025] Quinolones include quinolone-3-carboxylic acid and its analogs. Quinolones include a class of antibacterial agents that are analogs of hydroxylated quinolones and inhibit bacterial replication by inhibiting DNA (deoxyribonucleic acid) replication. Quinolones can be particularly used as chelating agents in a test environment such as the environment described herein because quinolones strongly bind to metal pollutants such as chromium, iron, or aluminum, etc., but weakly and reversibly bind to the analytes to be detected by the sensor in the test system or have no perceptible / detectable binding. Examples of such analytes to be detected include pH (hydronium ion), sodium, potassium, chlorine, hydrogen ion, carbon dioxide, glucose, lactate, creatine, creatinine, organic dyes, and / or alkaline earth metals such as calcium or magnesium, etc. For example, the order of the binding strength of quinolones with divalent ions is: Fe3+>Al3+>Cu2+>Fe2+>Zn2+>Mg2+>Ca2+, where the binding force with magnesium ions and calcium ions is weaker compared to the binding force with iron ions and aluminum ions. Strong chelation with the analytes to be detected will change their concentration, thus adversely affecting the measurement of these analytes by the sensor.

[0026] Different from quinolones, known chelating agents such as EDTA (ethylenediaminetetraacetic acid), tetraethylenepentamine (TETA), and nitrilotriacetic acid (NTA) strongly chelate with calcium, so they cannot be used to test certain types of analytes such as calcium, etc.

[0027] In addition, by adding a chelating agent to the composition, the oxygen concentration in the composition can be kept stable for a long time. Otherwise, the direct or mediated reaction with one or more trace metals will consume the oxygen in the composition and change the oxygen concentration, thus causing the oxygen in the composition to deviate from the known predetermined concentration. Therefore, the shelf life of the container (i.e., the length of time the container can be used for testing) can be increased compared to a container without a chelating agent in the composition. For example, the shelf life of a container containing a chelating agent can exceed 9 months, 10 months, 11 months, 12 months, or longer. Therefore, the test results using the composition in these containers can remain accurate for a long time and result in a longer shelf life compared to not containing these compositions.

[0028] In addition, since the sensor is in contact with the composition, the sensor may be affected by the chelating agent. However, the chelating agent in the composition does not interfere with the diffusion of the analyte through the external or internal sensor membrane. Examples of the external or internal sensor membrane that are not interfered with by the chelating agent may include, but are not limited to, a plasticized PVC membrane having valinomycin ionophore or ETH 1001 (which is a calcium ionophore for measuring potassium or calcium). In addition, the chelating agent in the composition does not react with the enzymes in the sensor (such as glucose oxidase, lactate oxidase, creatinine enzyme, creatine amidinohydrolase, or sarcosine oxidase). Therefore, the use of the chelating agent in the composition does not affect the operation of the sensor.

[0029] Figure 1 An example of a container 10 that can be used to store an exemplary composition 12 of the above type is shown. In this example, the composition 12 includes an aqueous liquid 13, one or more analytes 15, one or more chelating agents 16, and trace amounts of one or more types of metal ion contaminants 17.

[0030] Examples of the aqueous liquid 13 may include, but are not limited to, deionized water and a buffered or unbuffered aqueous liquid containing at least one of sodium chloride, potassium chloride, calcium chloride, glucose, or sodium lactate.

[0031] One or more analytes 15 include oxygen (O 2 ), and may further include, but are not limited to, one or more of the following: pH (hydronium ion), carbon dioxide (CO 2 ), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), magnesium (Mg), glucose (Glu), lactate (Lac), creatinine, creatinine, urea, organic dyes, amaranth, and sulforhodamine B. It can be understood that the analytes can be in ionic form or neutral form, depending on their stability and equilibrium state in the solution. The one or more analytes (including O 2 ) are dissolved in the aqueous liquid.

[0032] The metal contaminants 17 are not intended components of the composition but are contaminants. The metal contaminants may be trace metals at low concentrations, and their concentrations may be in the range of a few tens of parts per million (ppm) or parts per billion (ppb). Examples of metals that may constitute contaminants include, but are not limited to, chromium, iron, aluminum, cobalt, manganese, and copper. The outer electrons of metal atoms tend to be held more loosely than their inner electrons. Therefore, metal atoms tend to lose electrons. This electron loss causes the metal ions in the composition to be in various oxidation states, and in the absence of the chelating agent described herein, these metal ions combine with oxygen during the oxidation reaction, thereby consuming the oxygen in the composition. Metals in lower oxidation states, such as elemental forms or similar forms in steel sheets, also corrode and react with oxygen, thereby consuming the oxygen in the solution.

[0033] Examples of chelating agent 16 that may be included in the composition include, but are not limited to, compounds such as quinolone compounds. Examples of quinolone compounds that may be used as chelating agents in composition 12 include, but are not limited to, one or more of the following: levofloxacin, ciprofloxacin, gemifloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, enoxacin, amifloxacin, tosufloxacin, difloxacin, temafloxacin, miloxacin, cinoxacin, lomefloxacin, fleroxacin, fluoroquinolones, nalidixic acid, pipemidic acid, piromidic acid, rosoxacin, oxolinic acid, flumequine, enrofloxacin, sparfloxacin, gatifloxacin, balofloxacin, clinafloxacin, or sitafloxacin.In some embodiments, the chelating agent comprises one or more of the following: ciprofloxacin, gemifloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, enoxacin, amifloxacin, tosufloxacin, difloxacin, temafloxacin, miloxacin, cinoxacin, lomefloxacin, fleroxacin, fluoroquinolones, nalidixic acid, pipemidic acid, piromidic acid, rosoxacin, oxolinic acid, flumequine, enrofloxacin, sparfloxacin, gatifloxacin, balofloxacin, clinafloxacin, or sitafloxacin. In some embodiments, the chelating agent comprises levofloxacin alone or in combination with other chelating agents. In some embodiments, the composition may comprise a single quinolone compound. In some embodiments, the composition may comprise a combination of two or more quinolone compounds. In some embodiments, combinations of different quinolone compounds from the listed (or other) quinolone compounds may be used to chelate different metal contaminants.

[0034] In some embodiments, the total concentration of chelating agent 16 in composition 12 is greater than 60 milligrams per liter (mg / L). The total concentration in composition 12 is greater than 65 mg / L, the total concentration in composition 12 is greater than 70 mg / L, the total concentration in composition 12 is greater than 75 mg / L, the total concentration in composition 12 is greater than 80 mg / L, the total concentration in composition 12 is greater than 85 mg / L, the total concentration in composition 12 is greater than 90 mg / L, the total concentration in composition 12 is greater than 95 mg / L, the total concentration in composition 12 is greater than 100 mg / L, the total concentration in composition 12 is greater than 105 mg / L, the total concentration in composition 12 is greater than 110 mg / L, or the total concentration in composition 12 is greater than 115 mg / L.

[0035] In some embodiments, the total concentration of chelating agent 16 in composition 12 is less than 200 mg / L, the total concentration in composition 12 is from 60 mg / L to 120 mg / L, the total concentration in composition 12 is from 65 mg / L to 120 mg / L, the total concentration in composition 12 is from 70 mg / L to 120 mg / L, the total concentration in composition 12 is from 75 mg / L to 120 mg / L, the total concentration in composition 12 is from 80 mg / L to 120 mg / L, the total concentration in composition 12 is from 85 mg / L to 120 mg / L, the total concentration in composition 12 is from 90 mg / L to 120 mg / L, the total concentration in composition 12 is from 95 mg / L to 120 mg / L, the total concentration in composition 12 is from 100 mg / L to 120 mg / L, the total concentration in composition 12 is from 105 mg / L to 120 mg / L, the total concentration in composition 12 is from 110 mg / L to 120 mg / L, the total concentration in composition 12 is from 115 mg / L to 120 mg / L, the total concentration in composition 12 is from 60 mg / L to 80 mg / L, the total concentration in composition 12 is from 80 mg / L to 100 mg / L, or the total concentration in the composition is from 100 mg / L to 120 mg / L. In some embodiments, the total concentration of chelating agent 16 in composition 12 is up to 200 mg / L. Other embodiments may contain different total concentrations of quinolone compounds and / or quinolone analogs than those shown herein.

[0036] Different degrees of metal contamination can result in different oxygen consumption rates in composition 12. The above concentrations of chelating agent 16 in composition 12 may be advantageous because it / they are able to chelate without affecting the detection of the analyte. More specifically, quinolone compound 16 at concentrations significantly lower than the listed concentrations may not be able to chelate or may be insufficient to chelate metal contaminants in the composition to effectively prevent oxygen consumption, especially when the metal contaminant concentration in the composition is high, such as in the range of single-digit or double-digit parts per million (ppm). Chelating agent 16 at concentrations significantly higher than the listed concentrations may affect the behavior of the sensor used to detect the analyte in the test system. For example, significantly higher concentrations may alter the Ca and Mg concentrations in the composition and may inhibit the enzymatic function of an enzyme-based sensor or alter the composition and function of an ion-selective sensor.

[0037] The concentration of the chelating agent 16 listed can prevent, limit, or minimize oxidation in a composition containing metal contaminants, where the concentration of the metal contaminants is, for example, 10 ppb or higher, 20 ppb or higher, 30 ppb or higher, 40 ppb or higher, or 50 ppb or higher. In an example where the chelating agent is levofloxacin within the above concentration range in the composition, levofloxacin can prevent or limit oxidation in a composition containing metal ions, where the concentration of the metal ions is, for example, at least 10 ppb to 50 ppb.

[0038] Figure 2 A composition 12 is shown, which conceptually includes an aqueous liquid 13, a dissolved analyte 15, and metal ions 19 from a metal contaminant 17. The chelating agent 16 binds to the metal ions 19, thereby preventing the metal ions 19 from reacting with oxygen (one of the analytes 15 in this example).

[0039] Figure 3 A clinical analyzer 20 is shown, which is an example of a test system of the type described herein, and an example cartridge 23 used therewith. The clinical analyzer 20 can be configured to use sensors to measure one or more analytes in the composition 12 or a test sample, such as the analytes described herein. Examples of test samples include biological samples, such as body fluids like whole blood (“blood”) or its components or derivatives. Examples of such components or derivatives include, but are not limited to, plasma and a fluid containing red blood cells extracted from blood.

[0040] The clinical analyzer 20 includes a slot for receiving the cartridge 23. In some embodiments, the clinical analyzer 20 can include multiple slots (not shown), each for receiving a different instance of the cartridge 23.

[0041] The cartridge 23 includes one or more containers 30a to 30d each for containing an example of the composition 12, sensors 21 for sensing analytes in the test sample or the composition, and conduits 31a to 31d for moving the composition 12 from one of the containers 30a to 30d to the sensors 21. In some embodiments, the cartridge 23 can be a reusable cartridge. In some embodiments, the cartridge 23 can be a single-use, disposable cartridge.

[0042] Although Figure 3Four containers 30a to 30d are shown, but the cartridge 23 can contain fewer than four containers (e.g., one, two, or three containers) or more than four containers (e.g., five, six, seven, eight, etc. containers). The containers can be sealed bags or pouches. The bags or pouches can be made of laminated foil, soft plastic, rubber, or any other type of flexible liquid-tight and gas-tight material. In some embodiments, the containers can be made of hard plastic, glass, or any other type of rigid liquid-tight and gas-tight material. Each container can be a single-use, disposable container or a multi-use container.

[0043] Each container can contain a composition 12 of the type described above for Figure 1 and 2 The different containers can contain compositions having different analytes. For example, in some embodiments, each of the containers 30a to 30d can contain the same known, predetermined concentration of dissolved oxygen, but contain different other analytes. For example, container 30a can contain calcium but not magnesium, while container 30b can contain magnesium but not calcium. The different containers can contain compositions having different concentrations of the same analyte. For example, each of the containers 30a to 30d can contain a different known, predefined concentration of dissolved oxygen.

[0044] The clinical analyzer 20 can include one or more sensors 21 for testing the compositions and test samples described herein. In some embodiments, as shown, one or more sensors 21 can be part of one or more cartridges 23 housed in the clinical analyzer 20. In some embodiments, one or more sensors 21 are located within the clinical analyzer 20 and are not part of the cartridge 23 (not shown).

[0045] In some embodiments, exemplary sensors 21 include one or more enzymes, analyte-specific ionophores, or inert metal electrodes (such as platinum or gold, etc.), the composition of which can be specific to the particular analyte or analytes to be detected. Examples of sensors useful for the clinical analyzer 20 are described in U.S. Patent No. 6,872,297 (Mansouri), issued March 29, 2005, the content of which is incorporated herein by reference. Figure 3 The above-mentioned literature content is incorporated herein by reference.

[0046] The cartridge 23 includes exemplary conduits 31a to 31d, which can be fluidly connected to the sensor 21 through an exemplary tube 27 to transport the composition from the respective containers 30a to 30d so that the composition contacts the sensor 21.

[0047] During the operation of the clinical analyzer 20, the composition is moved (e.g., pumped) through the respective conduits from containers 30a to 30d onto the sensor 21. In an example of detecting oxygen, the sensor comprises an oxygen probe, which can be an inert metal electrode, such as a platinum electrode or the like. Oxygen measurement is performed by reducing oxygen to water or peroxide on the surface of the metal electrode. That is, when the metal electrode comes into contact with oxygen, a reduction reaction occurs between the oxygen on the platinum surface, producing water or hydrogen peroxide depending on the conditions. The transfer of electrons to the oxygen molecule generates an electrical signal on the platinum electrode, which is detected by an electrical detector of the clinical analyzer 20, and the clinical analyzer 20 uses the electrical signal to identify and measure the oxygen concentration in the composition. In some embodiments, the electrical detector includes a voltage measurer. For example, the voltage measurer can be a hardware device, such as a potentiometer electrically connected to the sensor 21 to measure voltage.

[0048] The foregoing operation of the clinical analyzer can be repeated for different components in containers 30a to 30d using the same sensor 21 or different sensors (e.g., electrode 21).

[0049] Experiment

[0050] Metal spiking

[0051] A process control solution (PCS) containing a composition similar to composition 12 but without the chelating agent is loaded into containers similar to those of a standard production batch. Subsequently, a second set of containers is filled with the PCS solution, and levofloxacin is added thereto. The starting metal content of each container is verified using ICP-MS (inductively coupled plasma mass spectrometry).

[0052] The tests included adding the following ions and concentrations to the containers: 50 ppb, 25 ppb, and 10 ppb of iron and copper ions (as shown in Table 1 below). The spiking experiment included adding known concentrations of trace metals to each container to achieve concentrations of 50 ppb, 25 ppb, and 10 ppb.

[0053]

[0054] Table 1

[0055] Iron Fe(II) was selected because iron is the most common metal ion contaminant in the composition due to device wear. Copper Cu(II) was selected because it consumes oxygen very rapidly at concentrations as low as 10 ppm. Fe(II) and Cu(II) were added to the containers, and then the containers were placed in an incubator at 37 °C for up to seven days. The oxygen decay was calculated by comparing the oxygen levels before and after exposure to the metal ions at 37 °C. In the experiment, the partial pressure of oxygen (ρO 2)Below -5.53 mmHg (millimeters of mercury) is considered a failed result, meaning that a value below -5.53 mmHg indicates unacceptable oxygen consumption within seven days. As shown in Table 1, levofloxacin provides significant antioxidant protection against up to 25 to 50 ppb of Fe(II) and 10 ppb of Cu(III).

[0056] Analyte stability

[0057] Container shelf-life tests were conducted to compare the shelf-life of containers containing the analyte and levofloxacin with that of control containers containing the analyte but no levofloxacin over 10.2 months. It was confirmed that the control containers had limited or no metal contamination. The storage temperatures were 15 °C and 25 °C. The focus of the experiment was to demonstrate that levofloxacin does not have an adverse effect on the shelf-life of the reagent and the analyte due to interaction with the listed analytes.

[0058] Table 2 below summarizes the shelf-life data for containers containing the composition stored at two temperatures, 15 °C and 25 °C. Over the 10.2-month test period, containers containing levofloxacin had no adverse effect on the listed analytes. Therefore, the time for each analyte to exceed the total allowable error (TEa) (confidence level of 95%) was greater than 10.2 months. The allowable TEa specifies the maximum amount of error (a combination of imprecision and bias) allowed for an analysis, and this error amount must be met for patient results to be suitable for use.

[0059]

[0060]

[0061] Table 2

[0062] Sensor stability and performance

[0063] To test the stability and performance of the sensor, the box life test was completed after one month of box shelf-life and then repeated after eight months of box shelf-life. The tests were conducted to demonstrate that the addition of levofloxacin to the composition does not affect Premier TM the assay performance of the 5000 system.

[0064] In addition, based on the parameter drift of the assays conducted on the Premier TM 5000 system, the PremierTM Reagent performance on the 5000 system. The drift of each assay parameter constitutes the deviation of the measurement result of each assay parameter from its factory-specified target. For example, during the use of the cartridge, Premier TM ρO was measured multiple times at defined frequencies on the 2 5000, and the drift of each measurement was calculated as the measured ρO of the composition 2 versus the ρO assigned to the composition at the time of manufacture 2 . This drift data was compared to demonstrate no difference in ρO 2 performance between compositions with and without levofloxacin.

[0065] Representative sensor drift data is presented as mean and standard deviation (SD) as follows to demonstrate that at one month and eight months shelf life, Premier TM 5000 sensors showed no adverse effects. More specifically, Table 3 shows the comparison for the one-month time period and Table 4 shows the comparison for the eight-month time period, where compositions made without levofloxacin are labeled "Control" and compositions made with levofloxacin are labeled "Levofloxacin". In this experiment, it was confirmed that the control containers had limited or no metal contamination (e.g., in parts per billion, cobalt 0.10, chromium 2.24, copper 0.64, iron 3.23, manganese 0.63). The limit column represents the maximum change that may occur during the shelf life of the composition according to Premier TM 5000 design specifications.

[0066] The data in Tables 3 and 4 show that compositions with and without levofloxacin perform similarly after one month and eight months of shelf life. Thus, the data in Tables 3 and 4 show that adding levofloxacin does not have an adverse effect on sensor performance and on the performance and stability of the composition for at least eight months of shelf life.

[0067]

[0068]

[0069] Table 3

[0070]

[0071]

[0072] Table 4

[0073] Whole blood

[0074] In Premier TM A whole blood method comparison study was conducted on the Premier 5000 system using raw and spiked (fortified) whole blood samples to validate sensor performance and ensure that levofloxacin does not affect the reported results.

[0075] In some embodiments, the compositions described herein (such as Figure 1 Composition 12 in

[0076] In some embodiments, the compositions described herein (such as Figure 1 Composition 12 in

[0077] The elements of the different embodiments may be combined to form other embodiments not specifically set forth previously. The elements may be excluded from the previously described systems without adversely affecting their operation or the operation of the overall system. Additionally, the various individual elements may be combined into one or more individual elements to perform the functions described in this specification.

[0078] Other embodiments not specifically described in this specification are also within the scope of the following claims.

Claims

1. A composition comprising: one or more analytes for use with an electrochemical sensor configured to detect a component of a biological sample; and Quinolone compounds, which are present in the composition at a concentration of 60 mg / L to 120 mg / L, are used to stabilize oxygen in the presence of trace metals.

2. The composition of claim 1, wherein the quinolone compound comprises a fluoroquinolone.

3. The composition of claim 1, wherein the quinolone compound comprises levofloxacin.

4. The composition of claim 1, wherein the quinolone compound comprises at least one of the following: ciprofloxacin, gemifloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, enoxacin, amifloxacin, tosufloxacin, difloxacin, temafloxacin, miloxacin, cinoxacin, lomefloxacin, fleroxacin, fluoroquinolones, nalidixic acid, pipemidic acid, piromidic acid, rosoxacin, oxolinic acid acid, flumequine, enrofloxacin, sparfloxacin, gatifloxacin, balofloxacin, clinafloxacin, or sitafloxacin.

5. The composition according to claim 1, further comprising: Aqueous liquid.

6. The composition of claim 5, wherein the trace metal comprises one or more metals.

7. The composition of claim 6, wherein the one or more metals are present in the composition at a concentration of 10 parts per billion (10 ppb) or greater.

8. The composition of claim 6, wherein the aqueous liquid contains dissolved oxygen; and wherein the one or more analytes further include: pH (hydrogen ion), carbon dioxide (CO2), oxygen (O2), sodium (Na), potassium (K), chloride (Cl), calcium (Ca), magnesium (Mg), glucose, lactic acid, creatinine, creatinine, urea, organic dyes, amaranth or sulforhodamine B.

9. The composition of claim 8, wherein the concentration of dissolved oxygen in the composition is known.

10. A container containing the composition according to claim 1.

11. The container of claim 10, wherein the container comprises a bag, a pouch or a glass.

12. The container of claim 10, wherein the container comprises a box.

13. A system comprising: A box comprising a plurality of containers, each of the plurality of containers containing a composition, each composition comprising: a liquid comprising one or more analytes; as well as A quinolone compound, wherein the concentration of the quinolone compound in the composition is 60 mg / L to 120 mg / L; wherein the liquids in different ones of the containers have different concentrations of the one or more analytes; and An electrochemical sensor configured to detect at least one of the analytes, the electrochemical sensor being located inside or outside the cartridge.

14. The system of claim 13, wherein the quinolone compound comprises levofloxacin.

15. The system of claim 13, wherein the quinolone compound comprises at least one of the following: ciprofloxacin, gemifloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, enoxacin, amifloxacin, tosufloxacin, difloxacin, temafloxacin, miloxacin, cinoxacin, lomefloxacin, fleroxacin, fluoroquinolones, nalidixic acid, pipemidic acid, piromidic acid, rosoxacin, oxolinic acid, acid, flumequine, enrofloxacin, sparfloxacin, gatifloxacin, balofloxacin, clinafloxacin, or sitafloxacin.

16. The system of claim 14, wherein the composition comprises one or more metals at a concentration of 10 parts per billion (ppb) or greater in the respective composition.

17. The system of claim 14, wherein the composition further comprises an aqueous liquid; and in, The aqueous liquid contains dissolved oxygen, which constitutes one of the analytes.

18. The system of claim 17, wherein: The one or more analytes also include: pH (hydrogen ion), carbon dioxide (CO2), oxygen (O2), sodium (Na), potassium (K), chloride (Cl), calcium (Ca), magnesium (Mg), glucose, lactic acid, organic dyes, sulforhodamine B or amaranth.

19. A kit comprising: an aqueous composition comprising one or more analytes for use with an electrochemical sensor configured to detect a component of a biological sample; and Quinolone compounds.

20. A method for measuring oxygen in the composition according to claim 1, the method comprising: contacting a surface of an inert metal electrode with the composition; and reducing oxygen at the surface; and generating an electrical signal, and detecting the electrical signal by a clinical analyzer; wherein the quinolone compound stabilizes oxygen in the composition prior to the oxygen measurement.

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