Abstract: AIM: To establish a simple, effective and sensitive LC-MS/MS assay to determine Indapamide in human plasma. METHODS: Diazepam was used as an internal standard. Human plasma samples were extracted by MTBE(tert-Butyl Methyl Ether).The separation was carried out on a Luna C₁₈ (150 mm×2.0 mm, 5 μm) column.The mobile phase consisted of 10 mmol/L ammonium formate with 0.1% formic acid:methanol (20∶80, V/V) at a flow rate of 0.30 mL/min. Electrospray ionization(ESI) source was applied and operated in the positive ion mode. The MS detection parameters were as follows: the source voltage was 3.5 KV and source temperature was 100 ℃. Quantitation was performed using multiple reaction monitoring(MRM) of the m/z 366.2→132.1 for Indapamide and 285.2→154.1 for diazepam.RESULTS: The liner calibration curves were obtained in the range of 0.536-45.733 ng/mL for Indapamide. The lower limit of quantification was 0.536 ng/mL.The mean relative recovery was 69%~81% and the relative standard deviation of the intra-day and inter-day precision of variation were less than 15%. By single and multiple doses studies, we can demonstrate that Indapamide sustained release tablets (1.5 mg/tablet) produced by Hunan Xieli Pharmaceutical Co.,Ltd and Servier(Tianjin) Pharmaceutical Co.,Ltd are bioequivalent. CONCLUSION: This method which is simple and sensitive can be used to determinate the concentration of Indapamide in human plasma.

Key words: LC-MS/MS, Indapamide, Pharmacokinetics, Bioequivalence