Quantitative analysis of dipeptidyl peptidase inhibitor P32/98 and its main metabolite in rat, dog, mouse, monkey, human plasma and human urine using liquid chromatography-tandem mass spectrometry: application to pharmacokinetic evaluation

A sensitive, specific and robust assay was developed for the simultaneous determination of the oral antidiabetic drug candidate P32/98 and its main metabolite P57/99 in different biological fluids using LC-MS/MS in the atmospheric pressure chemical ionization (APCI) positive mode. Both analytes were isolated from the biological matrices by solid phase extraction using a strong cation exchanger. This assay was successfully cross-validated for rat, dog, mouse, monkey, human plasma and human urine. The pre-study validation results, as well as the in-study quality control (QC) data obtained, demonstrate the feasibility of the assay for pharmacokinetic evaluation of the compounds in different species and confirm the robustness of the assay for routine use.