液相色谱-串联质谱法测定犬血浆中布地奈德  

LC-MS/MS determination of budesonide in dog plasma

作　　者：邓泮[1] 段小涛[1] 陈笑艳[1] 李三鸣[2] 钟大放[1] 

机构地区：[1]中国科学院上海药物研究所,上海201203 [2]沈阳药科大学,辽宁沈阳110016

出　　处：《药学学报》2008年第1期76-80,共5页Acta Pharmaceutica Sinica

摘　　要：建立液相色谱-串联质谱法测定犬血浆中布地奈德。血浆样品碱化后,经乙酸乙酯液-液萃取,以乙腈-5mmol.L-1醋酸铵(60∶40,v/v)为流动相,Capcell Pak C18MG柱分离;采用电喷雾电离源,以多反应监测(MRM)方式进行负离子检测,用于定量分析的离子反应分别为m/z489→m/z357(布地奈德)和m/z493→m/z413(内标,曲安奈德)。测定血浆中布地奈德方法的线性范围为25.0~2 000 pg.mL-1,定量下限为25.0 pg.mL-1,日内、日间精密度(RSD)均小于15%,准确度(RE)在-8.1%^-1.7%。应用本法研究6只比格犬单次和多次给予布地奈德缓释胶囊9 mg后的药代动力学结果显示:单次给药后Tmax为(3.5±3.3)h,Cmax为(786±498)pg.mL-1;多次给药后Cmax为(2 142±1 515)pg.mL-1。该法选择性强、灵敏度高、操作简便,适用于布地奈德缓释制剂的药代动力学研究。A liquid chromatographic-tandem mass spectrometric （LC-MS/MS） method was developed for the determination of budesonide in dog plasma. Budesonide and the internal standard triamcinolone acetonide were separated from plasma by alkalinized liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Capcell Pak ClS MG column with the mobile phase consisted of acetonitrile - 5 mmol· L^-1 ammonium acetate （60：40, v/v） at a flow-rate of 0. 50 mL·min^-1 A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring （MRM） of the transitions m/z 489→ m/z 357 and m/z 493→m/z 413 for budesonide and the internal standard, respectively. The linear calibration curves were obtained in the concentration range of 25.0 -2 000 pg. mL^-1. The lower limit of quantification was 25.0 pg·mL^-1 The intra- and inter-day relative standard deviation over the entire concentration range was less than 15 %. The accuracy was in the range of -8. 1% to - 1.7% in terms of relative error. The method was applied to a pharmacokinetic study of budesonide controlled-release capsules in Beagle dogs. Maximal budesonide plasma level was observed after （3.5 ± 3.3 ） h and the Cmax was （786±498 ） pg·mL^-1 after a single oral administration of 9 mg budesonide capsules, Cmax was increased to （2 142± 1 515） pg· mL^-1 after multiple oral administration （9 mg × 5 d） of budesonide capsules. This method was selective and rapid, and the sensitivity was sufficient for the purpose of the pharmacokinetic study of budesonide controlled-release formulation.

关 键 词：布地奈德 缓释制剂 液相色谱-串联质谱法 药代动力学 

分 类 号：R917[医药卫生—药物分析学]