Incurred sample reanalysis: dilemma in its applicability - should it be practiced for all bioanalytical assays involving single (parent or metabolite) or multiple analytes (parent/metabolite or parent with co-administered drugs)?

摘要

The intent of this note is to provide some perspectives and dilemma in the use of incurred sample reanalysis (ISR) in the real world.ISR has gained a lot of momentum in the last few years such that it is now being considered as an integral part of method validation procedure(s), especially when new assays for novel chemical entities (NCEs) and/or important drugs are being developed and marketed (Silvestro et al., 2010; Jemal et al., 2002, 2010; Zhang ef al., 2009, 2010b; Xu et al., 2009; Fast et al., 2009; Anderson et al., 2009; Myasein ef al., 2009; Wu et al., 2008; Huang et al., 2008; Rocci et al., 2007; Larsson and Han, 2007; Brockman et al., 2007). Recently, in a well-compiled report, discussions on the requirements of ISR for macromolecules, with appropriate statistical control, were eloquently presented (Thway et al., 2010). Interestingly, the same level of scrutiny for ISR seems to wither away as NCEs undergo further clinical development. It may be argued that ISR once established should support the analysis of the chosen NCE in the same matrix with all associated extraction/chromatographic/detection conditions and, hence, repetition of such analyses adds no value commensurate with expended resources. However, in some instances the assay(s) for parent NCE are significantly modified within the same matrix with the involvement of at least one of the following: (1) change in extraction system - liquid-liquid extraction converted to solid-phase extraction or vice versa; (2) altered chromatographic conditions - not merely change in flow rate and/or minor tweaking but change in the analytical column or quantitative change in the composition of mobile phase with changes in detection system; and (3) incorporation of other analytes such as key metabolites or co-administered drugs for quantitation under identical conditions as used before. While one needs to be pragmatic in making calls for the need for repeated ISR, it needs to be judicious and well thought-out, su...