When developing a quantitative LC-MS/MS method, ideally the standard curve and quality controls should be prepared in a matrix as similar as possible to the study samples to limit the potential for dissimilar matrix components to interfere with accurate quantification. However, if blank matrix is unobtainable, or if the analyte of interest is endogenous, then use of a surrogate matrix may be necessary.

The plasma ratio of caffeine/paraxanthine is used as a reliable indicator of the drug metabolizing enzyme CYP1A2. Similarly, coproporphyrin I/III are used as biomarkers of potential drug-drug interactions mediated by hepatic transport. The widespread use of caffeine makes obtaining drug-free plasma impractical, and coproporphyrin I/III are endogenous compounds. Therefore, we developed validated bioanalytical methods using surrogate matrices.

About the Presenter

Jason Watts, Ph.D., is a scientist at Alturas Analytics Inc. focusing on HPLC-MS/MS techniques for method development, validation, and sample analysis of new chemical entities and biomolecules utilizing a diverse background in molecular genetics, animal nutrition, and over a decade of mass spectrometry experience to provide innovative solutions to bioanalytical challenges.