摘要
目的建立一种测定人体血浆中吲哒帕胺浓度的HPLC-MS检测法,并对吲哒帕胺供试制剂与参比制剂进行生物等效性评价。方法血样经乙醚提取后,采用HPLC-MS法进行测定。色谱柱为Shim-pack ODS柱（5μm,150 mm×2.0 mm）,流动相为含0.04‰三乙胺和0.5 mmol.L^-1醋酸铵的水溶液与甲醇,检测离子为m/z364（吲哒帕胺）和m/z 275（内标氯磺丙脲）,裂解电压为25 V。20名健康志愿者交叉口服2.5 mg吲哒帕胺供试制剂和参比制剂,计算主要药动学参数及相对生物利用度,评价其生物等效性。结果在0.78-100.00μg.L^-1吲哒帕胺与内标峰面积比值与浓度线性关系良好（r=0.999 9）,定量限为0.78μg.L^-1,回收率为84.2%-93.8%。吲哒帕胺供试制剂相对于参比制剂的生物利用度为101.0±16.0%。结论该试验建立的分析方法灵敏、准确、简便。统计学结果表明两种制剂生物等效。
OBJECTIVE To develop an HPLC-MS assay for determination of indapamide in human plasma and to evaluate the bioavailability in healthy volunteers. METHODS Plasma was extracted with diethyl ether and separated by a C18 column with a mobile phase of methanol-water （ include 0.04 triethyl amine and 0.5 mmol L^-1 ammonium acetate）. HPLC-MS was performed in the selected ion monitoring mode using target ions at m/z 364 for indapamide and m/z 275 for chlorpropamide（IS）. The fragmentor voltage was 25 V. A randomized crossover design was carried in 20 healthy volunteers. In the two study periods, a single dose of 2.5 mg indapamide was administered to each volunteer. RESULTS The linear range was 0.78 - 100.00 μg·L^-1, r = 0.9999. The limit of determination was 0.78 μg·L^-1. The recovery was in the range of 84.2% -93.8%. The main pharmacokinetic parameters obtained showed no statistically significant difference between two preparations. CONCLUSION The assay was proved to be sensitive, accurate and convenient. Two products were bioequivalent.
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2007年第2期136-138,共3页
Chinese Journal of Modern Applied Pharmacy
