Bioanalytics – Chemical
2019 PharmSci 360
Bioanalytical method validation (BMV) of LC-MS/MS relies on the assessment of quality control samples in blank biologic matrixes (e.g. plasma). However, blank plasma used for BMV can significantly differ from in-study samples. Therefore, the potential interference of metabolite(s) might not be directly evaluated during BMV. In addition, many bio-analytical labs tend to use simple sample processing methods and short LC programs to increase throughput, which further increase the risk to specificity that may be caused by interfering metabolites.
Several case studies will be presented to show how 1) phase-II conjugate, 2) sulfate metabolite of phosphate prodrug and 3) isobaric phase-I metabolite, can affect the quantitation of parent drug. A discussion of good analytical practice which can reduce the possibility of metabolite interference, such as optimized LC separation, multiple MRM channels, precursor ions scan of whole LC chromatogram, and product ions scan of targeted peak in in-study samples.