Matrix effects in quantitative bioanalytical validations: are reproducible results all that is necessary?

“The analyte and/or IS signal can be altered by matrix effects in quantitative bioanalytical LC–MS/MS methods such that lot-to-lot differences in response factors impact data quality.” An important premise in quantitative analysis is that the response observed for each concentration of analyte (or IS), or the corresponding ratio analyte/IS, will be unique and independent of its origin, whether it was obtained from calibration standards, QCs or unknown samples. Prior to the use of LC–MS/MS for quantitative bioanalysis of small molecules, this premise held true for most bioanalytical methods, with the exception of possible sample-dependent quenching differences in some LC assays...