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

Abstract

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 C18 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.

Validation of a quantitative multiplex LC-MS/MS assay of carvedilol, enalaprilat, and perindoprilat in dried blood spots from heart failure patients and its cross validation with a plasma assay

“…In terms of determining adherence, the DBS concentrations can only be interpreted once converted to plasma concentrations. Pharmacokinetic data for carvedilol and enalaprilat are only available as plasma concentrations, whereas only one study is available with published whole blood pharmacokinetic data for perindoprilat [44] . Plasma concentrations are, therefore, significantly easier to interpret or evaluate in terms of adherence when compared to that of DBS concentrations, especially when modelling is implemented to interpret adherence according to weight and dose.…”

Chromatographic methods and approaches for bioequivalence study, drug screening and enantioseparation of indapamide

“…In 2018, Hang and associates [36] described assay of Indp and perindopril simultaneously after the European Hypertension Guidelines [37] suggested an update for combination of these two APIs as one of priority combinations of antihypertensive drugs. They reported a comparative pharmacokinetic study for the two in whole blood and plasma obtained from ten volunteers of good health in China.…”

Determination of amlodipine, indapamide and perindopril in human plasma by a novel LC–MS/MS method: Application to a bioequivalence study

“…Determination of AML in plasma alone or with other drugs was done by LC–MS/MS methods (Chen, Luan, Zhong, & Zong Min, 2001; Sathe, Venitz, & Lesko, 1999; Shah et al, 2017; Sirikatitham, Panrat, & Tanmanee, 2008; Streel, Lainé, Zimmer, Sibenaler, & Ceccato, 2002; B. Wang, Sheng, & Li, 2015; L. Wang, Liu, Zhang, & Tian, 2018; Wei, Yang, Qi, & Chen, 2009; Yacoub, Awwad, Alawi, & Arafat, 2013; Zheng, Wu, & Shao, 2006; Zou, Zhan, Ge, Wei, & Ouyang, 2009). Determination of IND in blood samples or plasma was reported (Ding, Yang, Liu, Ju, & Xiong, 2006; Pinto et al, 2014; Tao, Wang, Wang, Song, & Hang, 2018). PRN has been determined in human plasma alone or with other drugs by LC–MS/MS methods (El‐Bagary et al, 2017; Jain, Subbaiah, Sanyal, Pande, & Shrivastav, 2006; Nedogoda & Stojanov, 2017; Tao et al, 2018).…”

“…Determination of IND in blood samples or plasma was reported (Ding, Yang, Liu, Ju, & Xiong, 2006; Pinto et al, 2014; Tao, Wang, Wang, Song, & Hang, 2018). PRN has been determined in human plasma alone or with other drugs by LC–MS/MS methods (El‐Bagary et al, 2017; Jain, Subbaiah, Sanyal, Pande, & Shrivastav, 2006; Nedogoda & Stojanov, 2017; Tao et al, 2018). Searching the literature, there is no method for simultaneous determination of AML, IND and PRN in one sample of human plasma by HPLC–MS/MS.…”

“…The main problem with the IND analysis method is that it could be quantified in high concentrations only in blood samples, not in plasma. This may be due to its poor extraction recovery from plasma samples by the published methods (Gao et al, 2005; Pinto et al, 2014; Tao et al, 2018).…”