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

摘要

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 liquid chromatography-mass spectrometry (UPLC-MS/MS). Indapamide-d3, perindopril-d4 and perindoprilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C 18 column (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 independently 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 perindoprilat. 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.