Instrument Set-Up and System Suitability

System suitability checks should be performed before the first injection of the analytical batch and, for some methods, it is advisable to repeat this check when the analyses are completed. A detailed discussion of system suitability is given in Section 9.8.3, but the following description of a practical check procedure for LC-MS/MS systems has been found to be fit for purpose in many situations. 

To demonstrate that the LC-MS/MS system is performing with adequate sensitivity, that peaks are eluting at approximately the expected retention time(s) and that there is method appropriate instrument background, system suitability test injections followed by at least one blank injection should precede the sample run. The system suitability test and blank injections should be evaluated and documented as acceptable in the instrument notebook prior to injection of the run(s). In cases where several runs are injected in sequence, the system suitability may be used for aU runs in the sequence. Any significant disruptions between runs (e.g. system failure) would require a new system suitability assessment. The chromatograms for the system suitability and blank injections are generally not used to assess run acceptance but should be included with the sample run data. 

Examples of typical solutions to be used for system suitability checks are a standard solution (in clean solvent) containing the analyte(s) and internal standard(s) approximating the concentrations in a LLOQ or low QC sample, or an extracted calibration standard or QC at or near the LLOQ. Additional system suitability standards at concentrations at or near the ULOQ can be used to test for carryover at the beginning of the run. 

In some instances it may be necessary to inject one or more conditioning samples prior to the start of a chromatographic run for purposes of equilibrating the LC-MS/MS system. The conditioning samples may be derived from the run or may be separately extracted samples. Study 

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