Study on Pharmacokinetics of Indapamide in Chinese Volunteers

OBJECTIVE To develop a HPLC-ESI-MS for the determination of indapamide in human plasma and to investigate the pharmacokinetics of indapamide tablet in human.METHODS After being mixed with the internal standard glibenclamide and being acidized with hydrochloric acid solution,plasma samples were extracted with ethyl acetate and separated by HPLC on a C_(18) column with a mobile phase of methanol-10 mmol·L~(-1) ammonium acetate water solution(78∶22).LC-ESI-MS was performed in the selected ion monitoring mode using target ions at m/z 364.3 for indapamide and m/z 492.4 for internal standard.In the clinical trial,a single dose of 2.5 mg was administered orally to 20 healthy volunteers,and the pharmacokinetic parameters of indapamide were calculated.RESULTS Calibration curve for indapamide was linear over the range of 0.1～100 μg·L~(-1).The RSDs of intra-and inter-run were less than 9.4% and 10.6%,respectively.The ( )extraction recovery of indapamide in plasma was 90.5%～93.8%.The main pharmacokinetic parameters t_(1/2),t_(max) and ρ_(max) of indapamide in human were(18.2±4.3) h,(1.6±0.6) h and(55.8±8.4) μg·L~(-1),respectively.CONCLUSION The assay is proved to be sensitive,accurate and convenient.It can be applied to study the pharmacokinetics of indapamide formulations in humans.