吲达帕胺人体药动学研究

 目的建立人血浆中吲达帕胺的HPLC-ESI-MS测定法,以研究健康志愿者口服吲达帕胺片后吲达帕胺的药动学过程。方法血浆样品加入内标,以1 mol·L^-1的盐酸水溶液酸化后以乙酸乙酯萃取,进行HPLC-MS分析。色谱柱为Licrospher C₁₈,流动相为甲醇-10 mmol·L^-1醋酸铵水溶液(78∶22),内标为格列本脲,检测离子为m/z364.3(吲达帕胺)和m/z492.4(内标)。20名健康受试者po 2.5 mg吲达帕胺片,计算主要药动学参数。结果在0.1～100μg·L^-1内吲达帕胺与内标峰面积的比值与浓度的线性关系良好。批内RSD<9.4%,批间RSD<10.6%;提取回收率为90.5%～93.8%。吲达帕胺的消除半衰期为(18.2±4.3)h;峰质量浓度为(55.8±8.4)μg·L^-1;达峰时间为(1.6±0.6)h。结论本试验所建立的HPLC-ESI-MS分析方法快速、灵敏,可用于吲达帕胺人体药动学研究。

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 C₁₈ 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.