Method of calculating the lower limit of quantitation for mass spectrometry

Abstract

A method of determining a minimum concentration of a first analyte to be mass analysed in a mass spectrometer, comprising: (i) mass analysing a known concentration of said first analyte according to a

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority from and the benefit of United Kingdom patent application No. 2404411.7 filed on 27 March 2024, the entire contents of which are incorporated herein by reference. FIELD OF THE INVENTION The present invention relates generally to mass spectrometers and in particular to methods and mass spectrometers that determine the minimum concentration of an analyte that can be mass analysed whilst being able to reliably quantify that analyte. BACKGROUND In mass spectrometry analytes in a sample are mass analysed by being ionised and the resulting precursor ions, or fragment or product ions derived therefrom, are then detected in a mass analyser. For any given method of analysis of the analyte, it is only possible to reliably quantify the amount of analyte in the sample if more than a threshold amount of analyte is mass analysed. This means that for a given volume of sample being mass analysed, it is only possible to reliably quantify the amount of analyte in the sample if the analyte is present in a concentration that is at or above a certain level, known as the lower limit of quantitation (LLOQ). The concentration of an analyte that is the LLOQ is the concentration of that analyte that meets the following criteria: (i) provides a pre-selected signal to noise ratio (S / N) value for the ion signal detected when mass analysing the analyte; and (ii) provides a pre-selected relative standard deviation (RSD%) value for the ion signal. Conventionally it has been difficult and time consuming to determine the minimum concentration of an analyte that meets the RSD% requirement. SUMMARY From a first aspect the present invention provides a method of determining a minimum concentration of a first analyte to be mass analysed in a mass spectrometer, comprising: (i) mass analysing a known concentration of said first analyte according to a first mass analysis method using a mass spectrometer so as to obtain an ion signal having a peak; (ii) determining the number of ions detected by the mass spectrometer, during the first mass analysis method, to form said peak, Npeak; (Hi) determining the number of ions required to be detected in the ion peak in order for the peak to have a pre-selected relative standard deviation, Nreq; and (iv) determining the minimum concentration of the first analyte that can be mass analysed according to the first mass analysis method whilst achieving the pre-selected relative standard deviation, Crsd, based on the values of: said known concentration, Npeak and Nreq. As described elsewhere herein, it is only possible to reliably quantify the amount of analyte in a sample being mass analysed if more than a threshold amount of analyte is mass analysed. Said minimum concentration is the concentration of the first analyte that is required to be in the sample in order to achieve the pre-selected relative standard deviation when the volume of the sample that is mass analysed is the same as the volume that was mass analysed when determining said known concentration. If the volume of the actual sample to be mass analysed is higher than the volume that was mass analysed when determining said known concentration, then the concentration of the analyte in the actual sample to be mass analysed may be lower than said minimum concentration whilst still providing the threshold amount of analyte to the mass analyser in order to reliably quantify the amount of analyte in the sample. Conversely, if the volume of the actual sample to be mass analysed is lower than the volume that was mass analysed when determining said known concentration, then the concentration of the analyte in the actual sample to be mass analysed may be required to be higher than said minimum concentration in order to provide the threshold amount of analyte to the mass analyser in order to reliably quantify the amount of analyte in the sample. In instances where the volume of the actual sample to be mass analysed is different to the volume that was mass analysed when determining said known concentration, then the minimum concentration of the analyte in the actual sample to be mass analysed in order to reliably quantify the analyte may be determined by multiplying said known concentration by the volume that was mass analysed when determining said known concentration, and then dividing this product by the volume of the actual sample that is mass analysed. Step (ii) may comprise calculating the number of ions Npeak using the PT relationship Npeak oc A —; where A is the area of the peak; P is the number of instances that the first mass analysis method is performed during the peak; T is the duration that the first analyte is analysed according to the first mass analysis method during each instance that the first mass analysis method is performed; and W is the width of the peak at its base. Step (ii) may comprise calculating the number of ions Npeak according to Npeak = G(m)A—; where G(m) is a mass-dependent function that relates Npeak to — and where the value of G(m) depends on the mass or mass to charge ratio of the ion species that is detected at the ion detector during the first mass analysis method. Step (iii) may comprise calculating the number of ions Nreq according to Nreq = 1 +A2 (tyl) ---4^; where A(m) is a mass-dependent function and the value of A(m) depends on the RSDC mass or mass to charge ratio of the ion species that is detected at the ion detector during the first mass analysis method, and where RSDC is the value of said pre-selected relative standard deviation. The value of A(m), for a given mass or mass to charge ratio, is related to the relative standard deviation of a pulse-height distribution, RSDphd, of a given detector for ions of that mass or mass to charge ratio by: RSDphd — s / N Said known concentration of the first analyte is Cinj and step (iv) comprises determining said minimum concentration, Crsd, from: CRSD = -^-Cinj. Npeak The method may comprise determining a signal to noise ratio for the peak; selecting a minimum acceptable signal to noise ratio value for an ion peak when analysing the first analyte according to the first mass analysis method; and estimating a minimum concentration of the first analyte that can be mass analysed according to the first mass analysis method whilst achieving the minimum acceptable signal to noise ratio, Cs / n, by: multiplying said known concentration of said first analyte by said minimum acceptable signal to noise ratio value, and then dividing this by the determined signal to noise ratio. The mass spectrometer may automatically determine that the higher of Crsd and Cs / n is the minimum concentration of the first analyte to be mass analysed according to said first mass analysis method. The mass spectrometer may automatically display said determined minimum concentration on an electronic display. The method may comprise using a, or the, mass spectrometer to mass analyse a sample comprising said first analyte according to said first mass analysis method, wherein either: (i) said sample contains a lower concentration of the first analyte than said known concentration; or (ii) the volume of said sample that is mass analysed multiplied by the concentration of the first analyte in that sample is less than said known concentration multiplied by the volume that was mass analysed when determining said known concentration. The sample may only be mass analysed in this manner if it known to contain a concentration of the first analyte that is higher than the minimum concentration determined in the method described above (or if the volume of said sample that is mass analysed multiplied by the concentration of the first analyte in that sample is more than said minimum concentration multiplied by the volume that was mass analysed when determining said known concentration). The mass spectrometer may automatically adjust one or more of its operating conditions based on the determined value of Crsd and / or Cs / n, and perform the step of mass analysing said sample using the one or more adjusted operating conditions; or the mass spectrometer may automatically display information or options for adjusting one or more of its operating conditions based on the determined value of Crsd and / or Cs / n. The mass spectrometer may automatically adjust the one or more operating condition based on the determined value of Crsd, the determined value of Cs / n, or the determined higher value of Crsd and Cs / n. For example, the mass spectrometer may compare any one of these determined values to a target value and the mass spectrometer may automatically adjust said one or more operating condition based on that comparison. The step of automatically adjusting one or more operating condition of the mass spectrometer may comprise: a) adjusting the duration of time that the analyte is mass analysed according to said first mass analysis method during said step of mass analysing said sample; and / or b) adjusting a voltage applied to, or other operating condition of, one or more ion-optical elements that transmit ions through the mass spectrometer during said step of mass analysing said sample. For example, the duration of time that the first analyte is mass analysed according to said first mass analysis method during said step of mass analysing said sample may be increased. The method may comprise: selecting a target concentration of the first analyte that is desired to be mass analysed according to the first mass analysis method; determining the concentration Crsd, and optionally also Cs / n; and a) determining that the first analyte is able to be analysed according to the first mass analysis method if Crsd, and optionally also Cs / n, is below said target concentration; and / or b) determining that the first analyte is unable to be reliably analysed according to the first mass analysis method if Crsd and / or Cs / n is above the target concentration. The mass spectrometer may have a processor configured to automatically make this determination. The mass spectrometer may be configured to output the result of this determination on an electronic display. This method assumes that the volume of the sample to be mass analysed is the same as the volume that was analysed when determining the concentration Crsd and / or Cs / n. As described in relation to claim 1, if the volumes are different then the abovedescribed concentrations can be replaced by values representing the amount of the first analyte by multiplying each of the above-described concentrations by the respective volume of sample used when determining that concentration. The method may comprise separating a sample comprising different analytes using a chromatography device so that the different analytes elute from the chromatography device during different, respective chromatographic peaks; wherein step (i) is performed during the chromatographic peak for said first analyte, so as to obtain said ion signal having a peak. The chromatography device may be a liquid chromatography separator, or another type of separator such as a gas chromatography separator. Although a method has been described in which the minimum concentration of an analyte to be mass analysed according to a first mass analysis method is determined, it may also be desired to determine the minimum concentration of the first analyte to be mass analysed when it is being mass analysed according to a second, different mass analysis method. Accordingly, a method corresponding to that described above may be performed, except in relation to the first analyte being mass analysed by a second, different mass analysis method. The first and second mass analysis methods may be performed on the first analyte during the same chromatographic peak or instead in separate experiments. For example, the method may comprise: (i) mass analysing said known concentration of said first analyte according to a second, different mass analysis method during said chromatographic peak for the first analyte so as to obtain an ion signal having a peak; (ii) determining the number of ions detected by the mass spectrometer, during the second mass analysis method, to form said peak, Npeak; (Hi) determining the number of ions required to be detected in the ion peak in order for the peak to have a pre-selected relative standard deviation, Nreq; and (iv) determining the minimum concentration of the first analyte that can be mass analysed according to the second mass analysis method whilst still achieving the pre-selected relative standard deviation, Crsd, based on the values of: said known concentration, Npeak and Nreq. The analyte may be mass analysed by tandem mass spectrometry in said first and / or second mass analysis method. For example, the first analyte may be mass analysed by tandem mass spectrometry in which the mass spectrometer monitors a first multiple reaction monitoring (MRM) transition in the first mass analysis method and monitors a second MRM transition in the second mass analysis method. In other words, in the first mass analysis method the mass spectrometer may control a first mass filter so as to only transmit a single precursor ions species, control a fragmentation or reaction device to fragment or react that ion species so as to form fragment or product ion species, and to control a second mass filter to transmit a single one of the fragment or product ion species to an ion detector. In the second mass analysis method the mass spectrometer may control the first mass filter so as to only transmit a single precursor ions species (which may be the same or different to that transmitted in the first mass analysis method), control the fragmentation or reaction device to fragment or react that ion species so as to form fragment or product ion species, and to control the second mass filter to transmit a single one of the fragment or product ion species to an ion detector, wherein the fragment or product ion species transmitted by the second mass filter is different in the second mass analysis to in the first mass analysis. The mass spectrometer may repeatedly switch between the first and second mass analysis methods during the chromatographic peak for the first analyte. Although a method has been described in which the minimum concentration of an analyte to be mass analysed according to a first (and optionally also a second) mass analysis method is determined, it may be desired to determine such a minimum concentration to be mass analysed for each of multiple different analytes. This may be done in a corresponding manner to that described above. Accordingly, the method may determine a minimum concentration of a second different analyte to be mass analysed, comprising: (i) mass analysing a known concentration of said second analyte according to a further mass analysis method using the mass spectrometer so as to obtain an ion signal having a peak; (ii) determining the number of ions detected by the mass spectrometer, during the further mass analysis method, to form said peak, Npeak; (iii) determining the number of ions required to be detected in the ion peak in order for the peak to have a pre-selected relative standard deviation, Nreq; and (iv) determining the minimum concentration of the second analyte that can be mass analysed according to the further mass analysis method whilst still achieving the pre-selected relative standard deviation, Crsd, based on the values of: said known concentration, Npeak and Nreq. It may also be desired to determine the minimum concentration of that second analyte to be mass analysed when it is being mass analysed according to a yet further, different mass analysis method. This may be done in a corresponding manner to that described above in relation to the (first) analyte being mass analysed by the second mass analysis method. It will be appreciated that different analytes may co-elute from the chromatography device, i.e. they may have overlapping chromatographic peaks. Accordingly, the method may comprise determining a minimum concentration of a second different analyte to be mass analysed in the mass spectrometer, wherein the method comprising: (i) mass analysing a known concentration of said second analyte according to a further mass analysis method using the mass spectrometer so as to obtain an ion signal having a peak; (ii) determining the number of ions detected by the mass spectrometer, during the further mass analysis method, to form said peak, Npeak; (Hi) determining the number of ions required to be detected in the ion peak in order for the peak to have a pre-selected relative standard deviation, Nreq; and (iv) determining the minimum concentration of the second analyte that can be mass analysed according to the further mass analysis method whilst still achieving the pre-selected relative standard deviation, Crsd, based on the values of: said known concentration, Npeak and Nreq. The first and second analytes may be mass analysed by tandem mass spectrometry, where the mass spectrometer monitors a first multiple reaction monitoring (MRM) transition in the first mass analysis method and monitors a different multiple reaction monitoring (MRM) transition in the further mass analysis method; and wherein the mass spectrometer repeatedly switches between the first and further mass analysis methods during at least a portion of the time that the chromatographic peak for the first analyte overlaps with the chromatographic peak for the second analyte. The present invention also provides a mass spectrometer arranged and configured to perform the methods described herein. Accordingly, the first aspect of the present invention provides a mass spectrometer configured to execute the methods described above. The present invention provides a mass spectrometer that is configured to: (i) mass analyse a concentration of an analyte according to a first mass analysis method so as to obtain an ion signal having a peak; (ii) determine the number of ions detected by the mass spectrometer, during the first mass analysis method, to form said peak, Npeak; (iii) determine the number of ions required to be detected in the ion peak in order for the peak to have a pre-selected relative standard deviation, Nreq; and (iv) determine the minimum concentration of the first analyte that can be mass analysed according to the first mass analysis method whilst achieving the pre-selected relative standard deviation, Crsd, based on the values of: said concentration, Npeak and Nreq. The present invention also provides a computer-readable medium comprising instructions to cause the mass spectrometer to perform any of the methods described above. From a second aspect the present invention provides a method of mass spectrometry comprising: receiving an input indicating that a first analyte and a second analyte have been selected for mass analysis in a mass spectrometer that separates analytes using a chromatographic separator; determining that the first analyte is to be monitored for during a first time window and that the second analyte is to be monitored for during a second time window; determining that the first and second time windows overlap over a first time period; and determining the minimum duration of time that each of the first and second analytes is required to be analysed during this first time period in order to obtain a respective ion peak for each of the first and second analytes that meets a respective pre-selected condition. The method may control a user interface, such as an electronic display, to instruct the operator to adjust the mass spectrometer such that it analyses the first and second analytes for their determined minimum duration during the first time period. Alternatively, the method may automatically control the mass spectrometer to do this. The method may comprise separating the first and second analytes using the chromatographic separator; and analysing each of the first and second analytes for at least its respective minimum duration during said first time period so as to obtain a respective ion peak for each of the first and second analytes that meets its pre-selected condition. The first and second analytes are not able to be mass analysed by the mass spectrometer (i.e. detected) at the same time. Accordingly, during said first time period the mass spectrometer may repeatedly switch between: monitoring a first multiple reaction monitoring (MRM) transition when mass analysing the first analyte; and monitoring a second, different multiple reaction monitoring (MRM) transition when mass analysing the second analyte. The method may comprise: receiving an input indicating that a further analyte has been selected for mass analysis in the mass spectrometer; determining that the further analyte is to be monitored for during a further time window; determining that the further time window overlaps with the first and second time windows, over a second time period; and determining the minimum duration of time that each of the first, second and further analytes is required to be analysed during this second time period in order to obtain a respective ion peak for each of the first, second and further analytes that meets a respective pre-selected condition. The method may control a user interface, such as an electronic display, to instruct the operator to adjust the mass spectrometer such that it analyses the first, second and further analytes for their determined minimum duration during the second time period. Alternatively, the method may automatically control the mass spectrometer to do this. The method may comprise separating the first, second and further analytes using the chromatographic separator; and analysing each of the first, second and further analytes for at least its respective minimum duration during said second time period so as to obtain a respective ion peak for each of the first, second and further analytes that meets its preselected condition. According to embodiments, the first, second and further analytes are not able to be mass analysed by the mass spectrometer (i.e. detected) at the same time. During said second time period the mass spectrometer may repeatedly switch between: monitoring a first multiple reaction monitoring (MRM) transition when mass analysing the first analyte; monitoring a second, different multiple reaction monitoring (MRM) transition when mass analysing the second analyte; and monitoring a third, different multiple reaction monitoring (MRM) transition when mass analysing the further analyte. The method will determine that adding the further analyte to the analysis will decrease the duration of time available, during the second time period, to analyse the first and / or second analyte. Accordingly, the method will reduce the duration that the first and / or second analyte is analysed for during the second time period, relative to the corresponding time period prior to adding the further analyte to the analysis. However, the duration that the first and / or second analyte is analysed for, during the second time period, is reduced to a time that is still long enough for the respective ion peak to meet its preselected condition. The method may use one or more computer processors to perform each of the determination steps described. The method may be implemented on a mass spectrometer having such processors. A user may select the first and second analytes using an electronic user interface that, in response, provides said input. The user may also select said further analyte using the user interface. The one or more pre-selected condition may be a pre-selected signal to noise ratio for the ion peak; and / or the one or more pre-selected condition may be a relative standard deviation for the ion peak. The present invention also provides a computer-readable medium comprising instructions which, when executed on a computer, cause the mass spectrometer to carry out the methods described above. The computer may be a computer of a mass spectrometer. The second aspect of the present invention also provides a mass spectrometer arranged and configured to perform the methods described above in relation to the second aspect of the present invention. Accordingly, the present invention provides a mass spectrometer comprising a chromatographic separator and a mass analyser, wherein the mass spectrometer is configured to: receive an input indicating that a first analyte and a second analyte have been selected for mass analysis in the mass spectrometer; determine that the first analyte is to be monitored for during a first time window and that the second analyte is to be monitored for during a second time window; determine that the first and second time windows overlap over a first time period; and determine the minimum duration of time that each of the first and second analytes is required to be analysed during this first time period in order to obtain a respective ion peak for each of the first and second analytes that meets a respective pre-selected condition. The mass spectrometer comprises one or more processors and electronic circuitry configured to perform the determination steps described. From a third aspect the present invention provides a computer implemented method of determining whether to mass analyse an analyte in a mass spectrometer or whether an analyte can be reliably mass analysed in a mass spectrometer, the method comprising: receiving an input indicating that a first analyte has been selected for mass analysis in a mass spectrometer that separates analytes using a chromatographic separator; determining whether or not to mass analyse a further analyte, or whether the mass spectrometer is capable of reliably mass analysing the further analyte, by: i) determining that the first analyte is to be monitored for during a first time window and that the further analyte is to be monitored for during a second time window; ii) determining that the first and second time windows overlap over a first time period; iii) determining the duration of time that would be available to mass analyse each of the first analyte and / or further analyte during the first time period, if both the first and further analytes were selected to be mass analysed; iv) determining the minimum amount or minimum concentration of the first and / or further analyte that is required to be mass analysed in order to obtain a respective ion peak having one or more pre-selected condition, based on the determined duration of time that would be available to mass analyse the first and / or further analyte, respectively, during said first time period; and v) determining whether to mass analyse the further analyte, or whether the mass spectrometer is capable of reliably mass analysing the further analyte, based on a comparison of the determined minimum amount or minimum concentration of the first and / or further analyte with a pre-selected target amount or concentration for each of the first and / or further analyte, respectively. For example, it may be determined that if the further analyte was mass analysed then said minimum amount or concentration of the first analyte would increase above the target amount or concentration for the first analyte (as there is less time available to analyse the first analyte). Additionally, or alternatively, it may be determined that if the further analyte was mass analysed then said minimum amount or concentration of the further analyte would increase above the target amount or concentration for the further analyte (as there is less time available to analyse the further analyte). In such cases, it is determined that the further analyte is not capable of being reliably mass analysed or it should not be mass analysed. The method may use one or more computer processors to perform each of the determination steps described. The method may be implemented on a mass spectrometer having such processors. A user may select the first analyte using an electronic user interface that, in response, provides said input. The user may also select said further analyte using the user interface. The one or more pre-selected condition may be a pre-selected signal to noise ratio for the ion peak; and / or the one or more pre-selected condition may be a relative standard deviation for the ion peak. The minimum amount or concentration of the first and / or further analyte that is required to be mass analysed in order to obtain a respective ion peak having the one or more pre-selected condition may be determined according to the methods described herein in relation to the first aspect of the present invention, e.g. based on the calculations for Crsd and / or Cs / n. According to embodiments, the first and further analytes are not able to be mass analysed at the same time. In step iii) the duration of time that would be available to mass analyse the first analyte and / or further analyte may be determined based on the first and further analytes being mass analysed by tandem mass spectrometry, wherein the mass spectrometer repeatedly switches between monitoring a first multiple reaction monitoring (MRM) transition when mass analysing the first analyte and monitoring a different multiple reaction monitoring (MRM) transition when mass analysing the further analyte. It will be appreciated that the duration of time available to mass analyse each of the first and further analytes would be reduced by selecting the further analyte to be mass analysed. The present invention provides a computer-readable medium comprising instructions which, when executed on a computer, cause the mass spectrometer to carry out the methods described above. The computer may be a computer of a mass spectrometer. The present invention provides a method of mass spectrometry comprising: performing the method described above; and then separating a sample that includes said first and further analytes in a chromatographic separator; and either a) if it is determined in step v) to mass analyse the further analyte, then the method of mass spectrometry repeatedly switches between mass analysing the first analyte and the further analyte during the first time period; or b) if it is determined in step v) not to mass analyse the further analyte, then the method of mass spectrometry mass analyses the first analyte and not the further analyte during the first time period. The duration of elution of the first analyte from the chromatographic separator may overlap with the duration of elution of said further analyte from the chromatographic separator. In step a) the first and further analytes may be mass analysed by tandem mass spectrometry, where the mass spectrometer repeatedly switches between monitoring a first multiple reaction monitoring (MRM) transition when mass analysing the first analyte and monitoring a different multiple reaction monitoring (MRM) transition when mass analysing the further analyte. Although a method has been described in which a first analyte has been selected for mass analysis and it is determined whether or not to mass analyse a further analyte, it will be appreciated that the method may select a plurality of analytes to be mass analysed and then determine whether or not to mass analyse a further analyte. In such embodiments the method may determine that the further analyte is to be monitored for during a time window that overlaps with the time windows in which multiple selected analytes are monitored for. The above described method may then be performed for each of the multiple selected analytes. The third aspect of the present invention also provides a mass spectrometer arranged and configured to perform the methods described herein. Accordingly, the third aspect of the present invention provides a mass spectrometer configured to perform the method described above. The mass spectrometer comprises one or more processors and electronic circuitry configured to perform the determination steps described. BRIEF DESCRIPTION OF THE DRAWINGS Various embodiments will now be described, by way of example only, and with reference to the accompanying drawings in which: Fig. 1 shows an embodiment of a mass spectrometer according to the present invention; Fig. 2 illustrates an overview of an embodiment of the present invention for calculating the concentration of an analyte required to achieve an RSD% defined in the LLOQ; Fig. 3 shows an example of a chromatographic peak that has been sampled at multiple points; Fig. 4 shows examples of several pulse height distributions for ions of several different respective masses; Fig. 5 shows the probability density functions for the pulse height distributions shown in Fig. 4; Fig. 6 shows the ion signals detected for two different MRM transitions; Fig. 7 shows a table illustrating the analysis of several different analytes; and Fig. 8 shows an example of how adding an analyte to an analysis method can affect the LLOQ concentration for each of certain other analytes. DETAILED DESCRIPTION In mass spectrometry analytes in a sample are mass analysed by being ionised and the resulting precursor ions, or fragment or product ions derived therefrom, are then detected in a mass analyser. For any given method of analysis of the analyte, it is only possible to reliably quantify the amount of analyte in the sample if more than a threshold amount of analyte is mass analysed. This means that for a given volume of sample being mass analysed, it is only possible to reliably quantify the amount of analyte in the sample if the analyte is present in a concentration that is at or above a certain level, known as the lower limit of quantitation (LLOQ). The concentration of an analyte that is the LLOQ is the concentration of that analyte that meets the following criteria: (i) provides a pre-selected signal to noise ratio (S / N) value for the ion signal detected when mass analysing the analyte; and (ii) provides a pre-selected relative standard deviation (RSD%) value for the ion signal. The relative standard deviation discussed herein refers to the standard deviation in the areas of ion peaks that are detected for the same ion species in multiple different analyses of the same sample, divided by the average of those areas (and multiplied by 100 to obtain a percentage value). For example, in an MRM experiment the relative standard deviation is the standard deviation in the areas of ion peaks that are detected for the same MRM transition in multiple different analyses of the same sample, divided by the average of those areas (and multiplied by 100 to obtain a percentage value). A user may define the S / N and RSD% values that they require to be meet for the LLOQ concentration. The LLOQ concentration for each analyte of interest is typically determined when developing a method of analysing a sample in order to ensure that the sample being analysed contains each of the analytes of interest at a concentration that meets the LLOQ concentration for that analyte, so that it can be accurately quantified. For example, a user might define the LLOQ concentration of an analyte as the concentration of the analyte which both achieves a S / N of 5:1 and for which the RSD% is 10%. Currently, in order to calculate the S / N value for a LLOQ concentration of an analyte, a user will inject a sample that contains a relatively high concentration of the analyte into a mass spectrometer so as to mass analyse it, determine the height of a peak in an ion signal detected for the analyte, determine the baseline noise about the peak, determine the S / N value of the peak, and then use this S / N value to estimate the concentration of the analyte at which the ion peak will only just be detectable above the background noise or the concentration of the analyte that will meet a predetermined S / N value. For example, the S / N value that is required in order to meet the LLOQ condition may be defined by the user as 10:1. If the analyte is mass analysed and results in an ion peak having a S / N value of 1000:1, then mass analysing the analyte when it has a concentration that is 100 times lower could be expected to provide an ion peak having a S / N value of approximately 10:1, which is the S / N value required by the LLOQ. As such, the concentration for the analyte that is required to meet the S / N value defined by the LLOQ is determined to be a hundredth of the concentration of the analyte in the sample that was mass analysed. Similarly, if mass analysing the analyte provided an ion peak having a S / N value of 100:1, then if the sample was diluted 10 times it would be expected to provide an ion peak having a S / N value of approximately 10:1. Alternatively, if the height of the ion peak is determined to be 105 counts and the baseline noise is determined to be 103 counts, a user would be able to determine that they would not be able to inject the analyte at a concentration that is 100 times lower and still be able to distinguish the ion peak for that analyte from the noise. Therefore, it is relatively easy to determine the minimum concentration of a compound that will provide a S / N value that meets the requirements of the LLOQ. However, it has conventionally been difficult for a user to estimate the minimum concentration of the analyte that will meet the RSD% requirement of the LLOQ. Conventionally, in order to do this the user must prepare multiple diluted versions of the sample such that they have different concentrations of the analyte in them, mass analyse the analyte in each of these diluted samples multiple times, and then determine the RSD% for the ion signal for the analyte in each of the diluted samples. This must be done until a concentration is found that has an RSD% that meets the RSD% defined in the LLOQ. This concentration is then determined to be the lowest concentration of the analyte that could be reliably analysed in future experiments, whilst still expecting to meet the RSD% requirement of the desired LLOQ. It will be appreciated that this conventional process is extremely time consuming, especially considering that it may be desired to analyse hundreds of different analytes, and possibly also to analyse multiple different ion peaks for each analyte, such as by monitoring multiple MRM transitions for each analyte. Embodiments of the present invention provide an improved method of calculating the LLOQ concentration of an analyte for a given method of mass analysis. According to embodiments of the present invention, a sample is separated by a chromatography device, such as a liquid chromatography device, so that different analytes in the sample elute from the device over different respective time periods. The eluting analytes are then ionised and the resulting analyte ions are mass analysed by tandem mass spectrometry, also known as MS / MS. Fig. 1 shows an embodiment of a mass spectrometer according to the present invention. The spectrometer comprises a liquid chromatography device 2, an ion source 4, a first mass filter 6, a fragmentation or reaction device 8, a second mass filter 10, and an ion detector 12. As described above, a sample is injected into a liquid chromatography device, which causes the different analytes in the sample to elute over different respective time periods. The eluting analytes are ionised by the ion source, such as an electrospray ion source for example, so as to produce precursor ions. It will be appreciated that other types of ion source may be used instead. The precursor ions pass to the first mass filter, which is set to transmit only a narrow range of mass to charge ratios at any given time, e.g. corresponding to a single precursor ion species. This mass filter selects the analyte that is to be mass analysed. The precursor ions that are transmitted by the first mass filter pass to the fragmentation or reaction device and are fragmented, or reacted (e.g. with reactant ions or molecules), so as to form fragment or product ions. These fragment or product ions are then transmitted to the second mass filter, which is set to transmit only a narrow range of mass to charge ratios at any given time, e.g. corresponding to a single fragment or product ion species. The ions that are transmitted by the second mass filter strike the ion detector and produce an ion signal. The mass spectrometer may be operated so as to monitor for one or more Multiple Reaction Monitoring (MRM) transitions. When monitoring for an MRM transition the first mass filter is set to isolate a particular mass to charge ratio that is intended to correspond to a particular precursor ion species (i.e. from a particular analyte), and to transmit it to the fragmentation or reaction device. The second mass filter is set to isolate a particular mass to charge ratio that is intended to correspond to a particular fragment or product ion species, and to transmit that ion species to the ion detector. If ions are detected when the two mass filters are set in this manner then it can be determined with relatively high confidence what the precursor ions species is and therefore what the analyte is. As mentioned above, different analytes in a sample elute from the chromatography device over different respective timescales, i.e. as different chromatographic peaks. It may be desired to monitor more than one MRM transition for each analyte. When monitoring more than one MRM transition during a chromatographic peak for an analyte, the first mass filter is set to isolate and transmit a precursor ion species for the analyte and the second mass filter switches between isolating / transmitting different fragment / product ion species that correspond to the different respective MRM transitions. As will be described in more detail below, each MRM transition is monitored multiple times during each chromatographic peak, e.g. 10-15 times. As such, the second mass filter is set to transmit the fragment ion species for a particular MRM transition for only a short period of time, known as a dwell time, before switching to monitor the next MRM transition. Fig. 2 illustrates an overview of an embodiment of the present invention for calculating the concentration of an analyte required to achieve an RSD% defined in the LLOQ by the user, for a given method of analysis. In order to calculate this concentration, the embodiment uses: (i) the number of ions (Nreq) that are required to be detected in an ion peak, for said method of analysis, in order to meet the RSD% value for the LLOQ that has been defined by the user (RSDC); (ii) the number of ions detected in an ion peak (Npeak) for said method of analysis; and (iii) the known concentration of the analyte in the sample that is being analysed (i.e. injected into) the mass spectrometer Cinj. This method can be combined with the above-described methods to determine, and optionally display to the user, if the LLOQ concentration is limited by baseline noise, S / N or RSD%. As can be seen from Fig. 2, the embodiments uses various parameters to calculate the number of ions Nreq that are required to be detected in order to achieve the RSDC value. The number of ions Nreq that are required to be detected is determined based on a combination of the pulse height distribution and ion arrival statistics, as will be discussed in more detail further below. As mentioned above, in order to determine the concentration of an analyte that is required to be analysed in order to meet the user-defined RSD% value for the LLOQ, for a particular method of analysis such as for a particular MRM transition, the embodiments calculate the number of ions Npeak detected for that MRM transition during the chromatographic peak for the analyte. In a simple scenario the number of ions Npeak may be calculated from the ion peak based on the area of the peak. For example, the mass spectrometer may sample the ion signal by monitoring the MRM transition at multiple points during the elution of the analyte so as to ensure that the chromatographic peak is defined well enough for accurate integration, e.g. at 10-15 points. The ion signal reported for each data point of the peak is proportional to the ion counts per second. Fig. 3 shows an example of a chromatographic peak that has been sampled as described above at 13 points across the peak, as depicted by the vertical lines. If the mass spectrometer is operating so as to continually analyse only a single MRM transition during the chromatographic peak then the entire area under the peak could be determined and directly converted to number of ions Npeak. However, typically it is desired to analyse multiple different MRM transitions during an overlapping timescale. For example, it may be desirable to alternate between monitoring different MRM transitions of the same analyte during the chromatographic peak for that analyte. Additionally, or alternatively, different analytes may co-elute from the chromatography separation device and it may be desirable to alternate between monitoring different MRM transitions for the different respective analytes during the period that they co-elute. In such instances, the ions detected for any given MRM transition are only detected during portions of the chromatographic peak for its analyte. Therefore, to calculate the actual number of ions Npeak that are detected for a given MRM transition for an analyte during the chromatographic peak for that analyte, it is required to consider the number of times during the chromatographic peak that the ions for the MRM transition are detected and also the duration of each of these times. The shaded vertical bars within the peak in Fig. 3 represent the ion signal detected for a single MRM transition during the chromatographic peak. In this particular example, the MRM transition is monitored 13 times during the peak, although it will be appreciated that it may be monitored fewer times or a greater number of times. It will be appreciated from the above that the number of ions detected for an MRM transition during a chromatographic peak, Npeak, is related to the area of the chromatographic peak, the number of points during the peak that the MRM transition is monitored, and the duration that the MRM transition is monitored each of these time (i.e. the dwell time of the second mass filter). If the mass spectrometer uses a non-pulse counting detector, the contribution to the ion signal for a single ion may vary for ions having different masses or mass to charge ratios. It may therefore be advantageous to account for this when calculating the number of ions detected by applying an adjustment factor that is dependent on the mass or mass to chare ratio of the ion being detected. The actual number of ions counted for an MRM transition during a chromatographic peak, Npeak, can therefore be determined using the following formula: PT Npeak G(m)A where G(m) is a mass-dependent adjustment factor; A is the area of the chromatographic peak; P is the number of points across a peak that the MRM transition is monitored; T is the time that the MRM transition is monitored at each of these points (i.e. the dwell time of the second mass filter), in seconds; and W is width of the chromatographic peak as its base, in seconds. As described above, in addition to calculating the number of ions Npeak, the embodiments also calculate the minimum number of ions, Nreq, that are required to be detected in a chromatographic peak in order to achieve the RSD% defined by the LLOQ, i.e. to achieve RSDc. This theoretical minimum number of ions Nreq required to be detected to achieve a given RSDc is defined by a combination of ion arrival statistics and the effect of the pulse height distribution, as will be described below. The number of ions arriving at the detector in any given peak is based on ion arrival statistics and follows a Poisson distribution. The RSD of a Poisson distribution, RSDArr, is known and is given by the following equation, where N is the number of ions sampled: _ 1 RSDArr = > However, not all ions generate the same detector response when they strike the detector. More specifically, the ion detector produces an output pulse in response to an ion striking the detector, but these output pulses do not have a fixed intensity and instead follow a distribution of pulse heights known as a pulse height distribution. Fig. 4 shows examples of several pulse height distributions for ions of several different respective masses that were detected by a detector. Each pulse height distribution shows the number of ions (y-axis) striking the detector as a function of the detector pulse intensity that they produce (x-axis). As can be seen, each distribution is a peak, showing that a relatively large proportion of the ions each produce a similar output at the detector. Fig. 4 shows that ions having different masses may have different pulse height distributions and this is preferably taken into account when calculating Nreq. Fig. 5 shows the probability density functions for the pulse height distributions shown in Fig. 4. The probability density function for each mass represents the likelihood that an ion strike at the detector will generate each pulse intensity along the x-axis. The RSD due to the pulse height distribution, RSDphd, is given by the following equation, where A(m) is a mass-dependent function and N is the number of ions sampled: A(m) RSDphd = — As will be appreciated by the skilled person, the parameter A(m) may vary depending on the detector type and detector gain, but it is expected to be consistent on a given detector for each polarity of ion. The overall RSD of a peak is therefore defined by both RSDArr and RSDphd, and is obtained by adding these values in quadrature. Accordingly, the value of RSDc that is defined by the LLOQ is related to RSDArrand RSDphd as follows: RSDC2 = RSDArr2 + RSDphd2 Substituting each of RSDArrand RSDphd with their equations that are given above provides an equation for RSDc as follows: RSDC 1 + A2 (m) N The number of ions required to provide this RSDc, Nreq, is therefore given by: Nreq 1 + A2 (m) RSDr2 As described above, in order to determine the LLOQ concentration of an analyte, e.g. for a particular MRM transition, the embodiment uses: (i) the number of ions Nreq that are required to be detected during the analyte peak in order to achieve the RSDC value; (ii) the number of ions detected during the peak for the MRM transition Npeak; and (iii) the known concentration of the analyte that was injected Cinj to produce the peak. More specifically, because the number of ions counted in a chromatographic peak Npeak can be assumed to be proportional to the concentration of the analyte that was injected, the maximum factor D by which the analyte can be diluted whilst still expecting to meet the RSDc requirement of the LLOQ can be determined as: Npeak Nreq It is therefore possible to calculate the concentration Clloq that is required to meet the RSDc value of the LLOQ from the concentration of the analyte that was injected Cinj and the dilution factor D as follows: C _ ^inj CLLOQ ~ d As mentioned above, it is only possible to reliably quantify the amount of analyte in a sample being mass analysed if more than a threshold amount of analyte is mass analysed. It will be appreciated that the LLOQ concentration described herein is the concentration of the analyte that is required to be in the sample in order to meet the LLOQ when the volume of the sample that is mass analysed is the same as the volume that was mass analysed when determining said known concentration Cinj. If the volume of the sample to be mass analysed is higher than the volume that was mass analysed when determining said known concentration Cinj, then the concentration of the analyte in the sample to be mass analysed may be lower than Clloq whilst still providing the threshold amount of analyte to the mass analyser in order to reliably quantify the amount of analyte in the sample. Conversely, if the volume of the sample to be mass analysed is lower than the volume that was mass analysed when determining said known concentration Cinj, then the concentration of the analyte in the sample to be mass analysed may be required to be higher than Clloq in order to provide the threshold amount of analyte to the mass analyser in order to reliably quantify the amount of analyte in the sample. In instances where the volume of the sample to be mass analysed is different to the volume that was mass analysed when determining said known concentration Cinj, then the minimum concentration of the analyte in the sample to be mass analysed in order to reliably quantify the analyte may be determined by multiplying the known concentration Cinj by the volume that was mass analysed when determining said known concentration Cinj, and then dividing this product by the volume of the sample to be mass analysed. Examples of embodiments of the present invention will now be described with reference to Fig. 6. A tandem quadrupole mass spectrometer was used to perform tandem mass analysis of an analyte at a concentration of 1000 ppb in a manner as has been described above. The MRM transition of a precursor ion of the analyte having a mass to charge ratio of 305 Da to its fragment ion having a mass to charge ratio of 127 Da was monitored during the chromatographic peak for the analyte. In other words, the first mass filter was set to isolate / transmit ions having a mass to charge ratio of 305 Da, and the second mass filter was set to isolate / transmit ions having a mass to charge ratio of 127 Da. The spectrometer also analysed the MRM transition from this precursor ion to its fragment ion having a mass to charge ratio of 121 Da during the chromatographic peak. In other words, the first mass filter was set to isolate / transmit ions having a mass to charge ratio of 305 Da, and the second mass filter was set to isolate / transmit ions having a mass to charge ratio of 121 Da. Fig. 6 shows the ion signal detected for the fragment ion species having a mass to charge ratio of 127 Da and also the ion signal detected for the fragment ion species having a mass to charge ratio of 121 Da. The 127 Da ions were mass analysed at 13 points during the chromatographic peak by setting the second mass filter of the mass spectrometer at each of these points so as to only transmit the 127 Da ions to the detector. This is illustrated in Fig. 6 by the 13 intensity points that are located above the baseline. At each of these points in the chromatographic peak, the second mass filter was set to transmit the ions for a dwell time of 0.003 seconds. The area of the peak for the 127 Da ions was determined to have a value of 6.44x105 units and the width of the peak (at the base) was determined to be 7.08 seconds. The parameters A(m) and G(m) were calculated to be simple quadratic equations (with different values for each ion polarity). For the 127 Da ions, the value of A(m) was 5.76x10'1 and the value of G(m) was 8.25 x10'1. The equation for Npeak above was used to determine the number of 127 Da ions detected during the chromatographic peak. As is clear from above, the values of the parameters in the equation for Npeak are: G(m) = 8.25 x10'1; A = 1.045x105 units; P = 13; T = 0.003 s; and W = 7.08 s. The value for Npeak was therefore determined to be 475 ions. The equation for Nreq above was used to determine the number of 127 Da ions required to be detected during the chromatographic peak in order to meet the required value of RSDc that was defined by the user. As is clear from above, the value of A(m) to be used in the equation is 5.76x10'1. The value of RSDc was defined by the user as being 0.1 (i.e. 10%). Accordingly, using the equation for Nreq above it was determined that the number of 127 Da ions required to be detected during the chromatographic peak in order to meet the required value of RSDc was 133 ions. The value of Npeak divided by the value of Nreq was then calculated in order to determine the dilution factor D. As described above, the dilution factor is the factor by which the sample that was analysed can be diluted whilst still meeting the RSDc value defined by the user. The dilution factor D was therefore determined according to the equation above to be 3.57. The concentration of the analyte in the sample that was analysed, which gave rise to the 305 Da precursor ions (and ultimately the 127 Da fragment ions), was 1000 ppb. The concentration for this analyte that is required to meet the RSDc value, Clloq, was therefore obtained by dividing the sample concentration that was analysed (i.e. 1000 ppb) by 3.57 so as to provide a concentration of 280 ppb. The minimum concentration of the analyte required in the sample whilst still meeting the desired S / N ratio set by the user was also determined. The signal to noise value for the 127 Da peak in Fig. 6 was determined to be 28.3 (the noise has been removed from Fig. 6). The S / N value that was defined by the user in order to meet the LLOQ was S / N=10. As the S / N value determined for the injected sample was 28.3, it was recognised that the sample could be diluted 2.8 times before the S / N value would reach the value required by the LLOQ. Accordingly, it was determined that the minimum concentration of the analyte required in the sample to meet the S / N required by the LLOQ was 353 ppb (i.e. 1000ppb divided by 2.8). Accordingly, in this example for the 127 Da fragment ions, where the user defines the LLOQ as requiring an RSDc of 0.1 (i.e. 10%) and a S / N value of 10, the limiting factor on the LLOQ concentration is the required S / N value since a higher concentration of the analyte is required to achieve that than is required to achieve the RSDc value. As mentioned above, Fig. 6 also shows the ion signal detected for the fragment ion species having a mass to charge ratio of 121 Da. The 121 Da ions were mass analysed at 16 points during the chromatographic peak by setting the second mass filter of the mass spectrometer at each of these points so as to transmit the 121 Da ions to the detector. This is illustrated in Fig. 6 by the 16 intensity points that are located above the baseline. At each of these points in the chromatographic peak, the second mass filter was set to transmit the ions for a dwell time of 0.003 seconds. The area of the peak for the 121 Da ions was determined to have a value of 7.23x106 units and the width of the peak (at the base) was determined to be 8.82 seconds. The parameters A(m) and G(m) were calculated to be simple quadratic equations (with different values for each ion polarity). For the 121 Da ions, the value of A(m) was 5.74x10'1 and the value of G(m) was 8.23 x10'1. The equation for Npeak above was used to determine the number of 121 Da ions detected during the chromatographic peak. As is clear from above, the values of the parameters in the equation for Npeak are: G(m) = 8.23x10'1; A = 1.1737x106 units; P = 16; T = 0.003 s; and W = 8.82 s. The value for Npeak was therefore determined to be 5.25x103 ions. The equation for Nreq above was used to determine the number of 121 Da ions required to be detected during the chromatographic peak in order to meet the required value of RSDc that was defined by the user. As is clear from above, the value of A(m) to be used in the equation is 5.74x10'1. The value of RSDc was defined by the user as being 0.1 (i.e. 10%). Accordingly, using the equation for Nreq above it was determined that the number of 121 Da ions required to be detected during the chromatographic peak in order to meet the required value of RSDc was 133 ions. The value of Npeak divided by the value of Nreq was then calculated in order to determine the dilution factor D. As described above, the dilution factor is the factor by which the sample that was analysed can be diluted whilst still meeting the RSDc value defined by the user. The dilution factor D was therefore determined according to the equation above to be 39.5. The concentration of the analyte in the sample that was analysed, which gave rise to the 305 Da precursor ions (and ultimately the 121 Da fragment ions), was 1000 ppb. The concentration for this analyte that is required to meet the RSDc value, Clloq, was therefore obtained by dividing the sample concentration that was analysed (i.e. 1000 ppb) by 39.5 so as to provide an LLOQ concentration of 25 ppb. The minimum concentration of the analyte required in the sample whilst still meeting the desired S / N ratio set by the user was also determined. The signal to noise value for the 121 Da peak in Fig. 6 was determined to be 82.2 (the noise has been removed from Fig. 6). The S / N value that was defined by the user in order to meet the LLOQ was S / N=10. As the S / N value determined for the injected sample was 82.2, it was recognised that the sample could be diluted 8.22 times before the S / N value would reach the value required by the LLOQ. Accordingly, it was determined that the minimum concentration of the analyte required in the sample to meet the S / N defined in the LLOQ was 122 ppb (i.e. 1000ppb divided by 8.22). Accordingly, in this example for the 121 Da fragment ions, where the user defines the LLOQ as requiring an RSDc of 0.1 (i.e. 10%) and a S / N value of 10, the limiting factor on the LLOQ concentration is the required S / N value since a higher concentration of the sample is required to achieve that than is required to achieve the RSDc value. The embodiments of the present invention have various uses. For example, a user may need the LLOQ value for an analyte to be at or below a desirable target value. For instance, for pesticide analysis the user might want the LLOQ concentration for a pesticide analyte to be at or below a particular value, which may be, for example, five times lower than the minimum residue limit (MRL) for the pesticide. Embodiments of the present invention predict the LLOQ concentration required to achieve the user-defined RSDc value and / or to achieve the user-defined S / N value. One or both of these values may then be displayed to the user and / or compared with the target value, for example, as will be described in relation to Fig. 7. Fig. 7 shows a table illustrating the analysis of several different analytes. The first column indicates the analyte in the sample being analysed. The second column indicates the type of analysis, which is either quantitative or qualitative. The third column indicates the mass to charge ratio of the precursor ion of the analyte that is to be analysed. During the analysis the precursor ion is fragmented to form fragment ions and one or more of the fragment ions is analysed, i.e. an MRM transition is monitored. The fourth column indicates the mass to charge ratio of the fragment ion that is mass analysed. The fifth column indicates the average retention time of the analyte in the liquid chromatography separation device. The sixth column indicates the concentration of the analyte in the sample being analysed. The seventh column indicates the signal to noise ratio of the ion signal detected for the product ion during the chromatographic peak for the analyte. The eighth column indicates the baseline noise in the ion signal for the product ion. The ninth column indicates the area of the peak for the product ion. The tenth column indicates the concentration of the analyte that has been set as the desired threshold concentration, based on a factor unrelated to RSDc or S / N, and at which the LLOQ must be met. For example, this desired threshold concentration may be set to be five times lower that the minimum residue limit for each pesticide analyte. The penultimate column indicates the concentration of the analyte that is required in order to meet the S / N value that has been defined by the user in the LLOQ. For the examples shown in the table the S / N value defined by the user was 3:1 and the concentrations in the penultimate column were calculated according to the embodiments described herein. The final column indicates the minimum concentration of the analyte that is required in order to meet the RSDc value that has been defined by the user in the LLOQ. For the examples shown in the table the RSDc value defined by the user was 0.1 (i.e. 10%) and the concentrations in the final column were calculated according to the embodiments described herein. For each row in the table, i.e. for each MRM transition of an analyte, it can be seen that the concentration values in the final two columns may be below, at or above the concentration value in the third from last column. This enables the user to determine whether the analyte can be detected at the concentration in the third from final column (e.g. the minimum residue limit), whilst still meeting the LLOQ requirements for S / N and RSDc that have been set by the user. For example, the first row of data in the table shows that for the quantitative analysis of Acephate, using the MRM transition from 184.1 Da to 142.6 Da, it would be desired to analyse Acephate at concentrations down to 0.1 ppb (see third from final column). The final two columns of the table indicate the minimum concentration of Acephate that can be analysed whilst still meeting the S / N and RSDc requirements that have been set in the LLOQ by the user is 0.01 ppb. As such, it is apparent that it is possible to analyse this MRM transition of Acephate at concentrations down to the desired minimum concentration whilst still meeting the LLOQ that has been set by the user. In contrast, the seventh row of data in the table shows that it is not possible to analyse the exemplary MRM transition of Flonicamid at concentrations down to the desired minimum concentration whilst still meeting the LLOQ that has been set by the user. More specifically, the seventh row of data in the table shows that for the quantitative analysis of Flonicamid, using the MRM transition from 230 Da to 67.7 Da, it would be desired to be analyse Flonicamid at concentrations down to 0.01 ppb (see third from final column). However, the final two columns of the table indicate that the minimum concentration of Fipronil that can be analysed whilst still meeting the S / N and RSDc requirements that have been set by the user in the LLOQ are 1.76 ppb and 0.53 ppb, respectively. These values are significantly above the desired minimum concentration and hence indicate that an analysis at the desired minimum concentration would not provide detectable or reliable results, and that such an analysis could not be performed reliably. The mass spectrometer may be configured to automatically adjust its method of analysis for any given analyte (e.g. for any given MRM transition) so as to bring its LLOQ value(s) to be at or below the target concentration for that analyte. Alternatively, the mass spectrometer may be configured to automatically display information to an operator on how to adjust the operation of the spectrometer so as to bring the LLOQ value(s) to be at or below the target concentration for that analyte. For example, in either of these scenarios, if it is determined that the LLOQ value for a first analyte (or first MRM transition) is above its target concentration then the mass filter dwell time for analysing the first analyte (or first MRM transition) could be increased. If a second analyte (or second MRM transition, e.g. for the same analyte) is being analysed as part of the method, and the LLOQ value for that second analyte (or second MRM transition) is below the respective target concentration for that second analyte then the mass filter dwell time for analysing that second analyte (or second MRM transition) could be decreased so as to compensate for the increase in dwell time when analysing the first analyte (or first MRM transition). The decrease in dwell time is selected so as not to increase the LLOQ concentration for the second analyte (or second MRM transition) above its target value. Although the individual dwell times for the two analytes (or two MRM transitions) are changed, this may be controlled such that their combined duration does not increase and / or decrease. As mentioned above, different analytes in a sample typically elute from a chromatography separator as different chromatographic peaks. It may be desired to monitor one or more MRM transition for each analyte. When monitoring more than one MRM transition during a chromatographic peak, the second mass filter switches between monitoring the different MRM transitions and such that each MRM transition is monitored multiple times during each peak (typically 10-15 times as described above). Each time that an MRM transition is monitored, the second mass filter is set to transmit the fragment ion species for that MRM transition for a period known as a dwell time. The length of the dwell time that can be used depends on the number of different MRM transitions that must be monitored during the chromatographic peak. For example, if a greater number of MRM transitions must be monitored during each chromatographic peak then less time is available to monitor each MRM transition, i.e. the mass filter dwell time must be shorter. Furthermore, different analytes may elute from the chromatography separator during overlapping time periods, i.e. such that these different analytes elute with chromatographic peaks that overlap. Different MRM transitions will be required to be monitored for these different analytes. As such, during the elution times in which more chromatographic peaks overlap a greater number of MRM transitions will need to be monitored, whereas during the elution times in which fewer, or no, chromatographic peaks overlap a smaller number of MRM transitions will need to be monitored. It will therefore be appreciated that these factors influence the duration of the dwell time that the second mass filter can analyse any given instance of the MRM transition. When performing a method of analysis, it may be desired to change the number of MRM transitions monitored, e.g. by adding a new MRM transition to be monitored or removing one such that it is no longer monitored. For example, it may be desired to analyse an additional analyte and therefore at least one MRM transition for that new analyte will need to be monitored for. As described above, changing the number of MRM transitions that must be monitored during a given timescale changes the time available to monitor each MRM transition and therefore changes the dwell time that the second mass filter can analyse any given instance of a given MRM transition. This affects the sensitivity of the mass analysis, since changing the dwell time of the mass filter changes the number of ions that are transmitted for the MRM transition being analysed. This in turn will affect the concentration of the analyte that is required to meet the user defined LLOQ parameters. As the number of ions detected for a given MRM transition during a chromatographic peak, Npeak, is proportional to the dwell time used to analyse that MRM transition, the effect on the LLOQ concentration of changing the dwell time can be expressed as follows: lloqn ew LLOQOid Dwellpig Dwellnew where LLOQnsw is the new LLOQ concentration due to the change in dwell time; LLOQoid is the determined LLOQ concentration prior to the change in dwell time; Dwellnew is the dwell time after it has been changed; and Dwelloid is the dwell time before it has been changed. The mass spectrometer may be configured to add an additional MRM transition to an existing analysis method in which other MRM transitions are analysed. In order not to increase the overall analysis time for the MRM transitions, the dwell time for at least one of the MRM transitions from the existing method must be reduced. However, it can be seen from the above relationship that this will increase the LLOQ concentration for that MRM transition, whereas it may be desired to keep the LLOQ concentration below a target value for that MRM transition. The spectrometer may be configured such that when a new MRM transition is added to the analysis method the spectrometer automatically calculates a reduced dwell time for one or more of the other MRM transitions, e.g. using the above relationship, such that the new MRM transition is added to the analysis method without increasing the overall analysis time and without the LLOQ concentration for each MRM transition increasing above its respective target value. The spectrometer may be configured to automatically adjust the dwell times for the MRM transitions based on this calculation during the analysis, or it may be configured to automatically display information to an operator on how to adjust the operation of the spectrometer to do this. Alternatively, the above-described method could be used to assess the likely impact of adding an analyte to, or removing an analyte from, the analysis method. A decision can then be made as to whether that analyte should be, for example, added to the analysis based on the change that this would cause to the LLOQ concentration of that analyte, or that this would cause to the LLOQ concentration of one or more of the other analytes being analysed in the method. For example, if adding the analyte to the analysis would result in that analyte, or another of the analytes, having a respective LLOQ concentration that is above its target value then the spectrometer could indicate this and optionally that the analyte should not be added to the analysis. Even if the value of LLOQoid is not known for the analyte proposed to be added to the method of analysis, this technique may still be used to determine the factor by which the LLOQ would be expected to change (i.e. by a factor of Dwelloid divided by Dwellnew) for each of the other analytes. Fig. 8 shows an example of how adding an analyte to an analysis method can affect the LLOQ concentration for each of certain other analytes. Fig. 8 shows a list of MRM transitions that the method is set to analyse. Each row relates to a different analyte, e.g. the first row relates to Dilantin and the second row relates to Metformin. Each row also indicates the number of MRM transitions that are to be monitored for the analyte, e.g. two MRM transitions are monitored for Dilantin. Each row indicates elution time of the analyte from the chromatography device, e.g. the first row indicates that Dilantin elutes over the period from 0.7 to 2.50 mins. The elution times of the analytes are also shown graphically as horizontal bars on the right side of Fig. 8 and it can be seen that many of the analytes have overlapping elution times, i.e. overlapping chromatographic peaks. It can be seen from Fig. 8 that if an analyte is added to the analysis that has a range of elution times that overlaps with a range of elution times of one or more other analytes then this will affect the number of MRM transitions that must be monitored during that overlapping time period. Similarly, if an analyte was removed from the analysis that has a range of elution times that overlaps with a range of elution times of one or more other analytes then this will affect the number of MRM transitions that must be monitored during that overlapping time period. For example, it can be seen from Fig. 8 that if the analyte ibuprofen was added to the method of analysis then this would affect the time available to analyse all of the analytes that are encompassed by the vertical arrow, because they all have elution times that overlap with that of ibuprofen. For this subset of analytes, the dwell time of the second mass filter that is used in each instance of each MRM transition analysis would be automatically reduced, e.g. in order to maintain a given number of analysis points for each analyte during its chromatographic peak. This reduces the number of ions that are counted for each MRM transition in each chromatographic peak, which changes the LLOQ concentration for each of analyte. The effect of this on the LLOQ concentration of each analyte can be determined, as described above, and used to determine if the analysis of ibuprofen should be added to the method or not. Alternatively, as described above, the mass spectrometer may automatically reduce the dwell time for one or more of the analytes, in the subset of analytes, in a manner such that its LLOQ concentration does not rise above its respective target value. Although the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims. For example, although techniques for use in determining the LLOQ concentration of an analyte that meets the RSD% requirement based on Npeak and Nreq have been described herein, additional considerations that affect the RSD% may also be taken into account when determining the concentration of the analyte to be mass analysed. For instance, variability in the sample injection to the mass spectrometer from the chromatography system may increase the LLOQ concentration. Accordingly, the technique described herein may be used as a guide, along with other considerations, when determining the minimum concentration of the analyte to analysed (for a given sample volume) during the method development process. Additionally, or alternatively, although the analytes have been described as being analysed by tandem mass spectrometry, it is contemplated that other methods of mass analysis may be used instead.

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