Simultaneous determination of indapamide, perindopril and perindoprilat in human plasma or whole blood by UPLC-MS/MS and its pharmacokinetic application

Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by hyphenated ultra-performance li-quid chromatography-mass spectrometry (UPLC-MS/MS). Indapamide-d3, perindopril-d4 and perindo-prilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C18column (4.6 mm × 100 mm, 2.4 μm) for indapamide and perindopril simultaneously following a protein precipitation pretreatment of the biosamples. The separation of perindoprilat was achieved in-dependently on a phenomenex PFP column (4.6 mm × 150 mm, 5 μm). All the analytes were quantitated with positive electrospray ionization and multiple reactions monitoring mode. The assay exhibited a linear range of 1–250 ng/mL for indapamide, 0.4–100 ng/mL for perindopril and 0.2–20 ng/mL for peri-ndoprilat. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to the pharmacokinetic study of perindopril tert-butylamine/indapamide compound tablets in Chinese healthy volunteers and the comparative pharmacokinetic study between plasma and whole blood.