Using the Control Matrix to Assess Selectivity

In the biomedical context another check can involve comparison of LC-MS and/or LC-MS/MS chromatograms obtained for control matrix spiked with analytical standard with those obtained for incurred samples, i.e. post-dose samples from the same individual (human or lab animal) as that from which the control matrix was obtained. In this way the presence of metabolites and/or of matrix components that are peculiar to the test subject (individual) can sometimes be detected (see below). When several different control matrices from different sources are available, it can be useful to compare chromatograms from the individual control matrices with that obtained for a pool (mixture) of aU of them, since this comparison can highlight regions in the chromatogram that are potentially problematic as a consequence of variations in matrix composition. If undetected, such variations in matrix composition can give rise to false positive identifications or to quantitative results that are significantly in error. 

In view of the potential problems summarized in the preceding paragraph, if it becomes necessary to obtain additional control matrix part way through a study (a series of analyses of samples from a complete study. 

The benefits of further validation of a bioanalytical method by judicious use of incurred samples have been described (Jemal 2002), with particular emphasis on detection of contributions of formerly undetected coeluting metabolites to signal intensity in the SIM or MRM channels used to monitor the target analyte and/or the SIS Table 9.4 summarizes accumulated experience permitting prediction of metabolite types resulting from specific functional groups in the analyte. Such spurious contributions (direct interferences, not matrix effects) will be absent from the samples prepared from control matrix spiked with analytical standard and used for the validation procedures and as QC samples. The following sequence of checks was recommended (Jemal 2002)  

Another potential complication (Matuszewski 1998 Jemal 2002) arising from metabolites in incmred samples 

Functional group in Metabolite and mass CID reactions of metaboUte Potential for metaboUte to 

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