Simultaneous determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma using...

Lots of studies showed the combination therapy of perindopril, indapamide and amlodipine could increase BP lowering efficacy and the benefits of high-risk patients. To evaluate potential pharmacokinetic interaction, a simultaneous UPLC-MS/MS quantification method of perindopril, perindoprilat and indapamide in human plasma was developed and validated. The plasma samples were prepared by solid phase extraction, and then separated on an X-terra MS C₁₈ (2.1 mm × 150 mm, 3.5 μm) with isocratic elution. The ion transitions at m/z 369.165 → 172.000 (perindopril), m/z 341.146 → 170.112 (perindoprilat), m/z 366.010 → 132.100 (indapamide), m/z 389.120 → 206.200 (S10211-1, IS1) and m/z 394.080 → 160.200 (S1641, IS2) were monitored under the positive ion mode of electrospray ionization with multiple reaction monitoring. This method exhibited great sensitivity, linearity, accuracy, and precision for the determination of perindopril, perindoprilat and indapamide over the range of 0.250-50.0 ng/mL. The average extraction recovery of perindopril, perindoprilat and indapamide samples at low, medium, and high concentration levels were between 85.9% and 93.6%, respectively. The stability of analytes over different storage and processing conditions in the whole study was also validated. The method is fast, accurate, sensitive and reproducible, which is suitable for the detection of the concentration of perindopril, perindoprilat and indapamide in human plasma.