高效液相色谱-串联质谱法测定人血浆中吲哒帕胺及其生物等效性研究

Determination of indapamide in human plasma with high performance liquid chromatography-mass spectrometry method and bioequivalence study

目的:研究用高效液相色谱-串联质谱(HPLC-MS)法进行试验制剂吲哒帕胺片剂与参比制剂市售吲哒帕胺片剂生物等效性研究。方法:男性健康志愿者20名,随机分为2组,分别交叉单剂服用受试制剂或参比制剂吲哒帕胺片剂2．5 mg,采用HPLC-MS法,选择正离子检测的大气压化学电离源(APCI源),以甲醇-1％甲酸水溶液(75:25,V／V)为流动相,测定吲哒帕胺血药浓度,计算药动学参数,评价2制剂的生物等效性。结果:受试制剂和参比制剂主要药动学参数tmax为(1．4±s 0．4)和(1．4±0．4)h, Cmax为(30±6)和(30±5)μg·L-1,t1／2为(14．7±2．1)和(14．3±2．5)h,AUC0-72为(539±103)和(534±95)μg·h·L-1,AUC0-∞为(570±105)和(565±98)μg·h·L-1。受试制剂吲哒帕胺片剂相对生物利用度(F)为(102±13)％。结论:该方法选择性强、灵敏度高、操作简便,适用于吲哒帕胺制剂的生物等效性评价及临床药动学研究。

AIM： To study the bioequivalene of indapamide tablets and market available indapamide tablets with high performance liquid chromatography-mass spectrometry （HPLC-MS） method in healthy volunteers. METHODS： Twenty male healthy volunteers were randomly divided into 2 groups （test preparation group and reference preparation group）, ten for each and undertaken two cross-over designs. Plasma concentrations were determined by HPLC-MS method after a single oral dose of 2.5 mg individually of test indapamide tablets or the reference ones, respectively. The mobile phase consisted of methanol-1% formic acid （75 ： 25, V/V）, and detection was performed on a single quadrupole mass spectrometer in positive selected ion monitoring （SIM） mode via atmospheric pressure chemical ionization （APCI） source, The plasma concentrations, pharmacokinetics and bioequivalencc of the two preparations were measured and calculated. RESULTS. The pharmacokinetic parameters of indapamide tablets of test and reference were as follows： tmax= （ 1.4± s 0.4） and （1.4 ± 0.4） h; tl/2= （14.7± 2.1） and （14.3±2.5） h; cmax= （30±6） and （30 ± 5） μg·L^-1; AUC0-72 = （539±103） and （534±95）μg·h·L^-1; AUC0-∞= （570±105） and （565±98）μg·h·L^-1. The relative bioavailability of the test indapamide tablets was （102±13） %. CONCLUSION： HPLC-MS method is selective, sensitive and convenient, proved to be suitable for bioequivalence evaluation of different formulations for indapamide and also for clinical investigation of indapamide pharmacokinetics.