Regulated bioanalysis

Chang, M. S., Kim, E. J., and El-Shourbagy, T. A. (2007b). Evaluation of 384-well formatted sample preparation technologies for regulated bioanalysis. Rapid Commun. Mass Spectrom. 21 64-72. 

From a practical point of view, internal standard in a LC-MS/MS assay serves three distinct purposes in the analytical process. The first purpose is to compensate extraction recovery inconsistencies. The second purpose is to compensate injection volume variation. The third purpose is to compensate possible matrix effects during the MS ionization process as has already been discussed in detail above. In 2009, Tan A. et al. reported 12 case studies from incurred sample analyses using a wide variety of bioanalytical methods for the investigation of inconsistent internal standard response [23], For similar reasons, it has now become common for laboratory SOPs to contain specific requirements for the acceptable internal standard response of each individual sample within a sample batch during regulated bioanalysis. These requirements (e.g., 60-140 %, 50-150 % of the average internal standard area for all samples in the batch) ensure that the behavior of the internal standard, regardless of how well it tracks the analyte, is under control, and is consistent in all samples. 

Fung,E.N.,Xia,Y.Q.,Aubry,A.F.,Zeng,I,Qlah,T.,Jemal, M. (2011) Full-scan high resolution accurate mass spectrometry (HRMS) in regulated bioanalysis LC-HRMS for the quantitation of prednisone and prednisolone in human plasma./owma/ of Chromatography B Analytical Technologies in the Biomedical and Life Sciences,879 Tl), 2919-2927. 

Initially, when the number of compounds and samples is high, method quality can be balanced by the need for speed. The risk of a potentially incorrect decision based on low-quality bioanalysis is much more manageable in early discovery, particularly because this phase is not regulated but is for decision making and candidate selection purposes only. Expectations for method quality are generally lower for in vitro samples than those from in vivo studies. This is due in part to the amount of effort required to synthesize the relatively modest amount of compound for an in vitro experiment compared to the amount necessary to dose animals and also due to the complexity of the sample matrix, which is much simpler for in vitro samples than in vivo samples such as plasma or tissue. 

Method Development, Validation, and Sample Analysis for Regulated Quantitative Bioanalysis Using LC-MS/MS... 

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