A fully automated and validated human plasma LC-MS/MS assay for endogenous OATP biomarkers coproporphyrin-I and coproporphyrin-III

A validated LC-MS/MS assay for the quantitation of coproporphyrin-I and -III (CP-I, CP-III) in human plasma has been developed to understand the utility of both as possible endogenous biomarkers for organic anion-transporting polypeptides (OATP)-mediated drug-drug interactions (DDIs). Human plasma extracts were analyzed for CP-I and CP-III using a 6500+ mass spectrometer. The assay was utilized for plasma samples from a clinical DDI study involving a new chemical entity that presented as an OATP inhibitor . A formal DDI study, with a probe drug (atorvastatin), was also included as part of the clinical study. Changes in CP-I plasma area under the plasma concentration versus time curve (AUC ) were observed, which were similar to the AUC ratio obtained with atorvastatin. These results support the idea that plasma CP-I may have utility in Phase I by supporting the rapid assessment of OATP inhibition risk.