LC-MS/MS法测定人血浆中戊乙奎醚的浓度及其药动学的应用  

Determination of penehyclidine in human plasma by LC-MS/MS and its application in pharmacokinetics study

作　　者：冯仕银[1] 雍小兰[1] 黄娟[1] 李楠[1] 王蓝天[1] 杜晓琳[1] 

机构地区：[1]中国人民解放军成都军区总医院临床药学科,成都610083

出　　处：《药物分析杂志》2016年第1期111-116,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:采用LC-MS/MS法测定人血浆中戊乙奎醚的浓度,并应用于人体药代动力学的研究。方法:血浆样品经氢氧化钠碱化,固相萃取后进行分析。使用Agilent C_(18)(150 mm×4.6 mm,5μm)色谱柱,流动相为5 mmol·L^(-1)醋酸铵(用甲酸调pH 5.58)-甲醇(35:65),流速1 mL·min^(-1);ESI离子源,多反应离子监测,用于定量分析的离子对为m/z 316.2→110.3(戊乙奎醚)和m/z 256.2→167.2(苯海拉明)。结果:戊乙奎醚的线性范围为0.10~8.00 ng·mL^(-1),最低定量限为0.10 ng·mL^(-1);萃取回收率为85.8%~99.9%,基质效应为79.7%~93.2%;日内和日间RSD均<11.1%。3个剂量戊乙奎醚的主要药代动力学参数:C_(max)分别为(2.65±1.06)、(4.88±3.14)和(5.93±1.83)ng·mL^(-1);t_(1/2)分别为(29.35±13.56)、(25.22±8.71)和(26.41±6.81)h;AUC_(0-t)分别为(71.81±44.02)、(93.89±65.14)和(106.50±53.01)h·ng·mL^(-1)。结论:本法经方法学验证,适用于人血浆中药物浓度的测定,受试者口服0.4、0.6和0.8 mg盐酸戊乙奎醚片后的药代动力学参数呈线性。Objective： To develop an LC-MS/MS method for determination of penehyclidine in human plasma, and further apply the method in pharmacokinetics study. Methods： Penehyclidine and internal standard diphenhydramine were extracted from plasma after alkalization by sodium hydroxide, and then separated on an Agilent Cls （ 150 mm × 4.6 mm, 5 μ m ）column. The mobile phase consisted of methanol and 5 mmol· L^-1 ammonium acetate （ 65 ： 35 ） with isocratic elution at a flow rate of 1.0 mL· min^-1. Electrospray ionization （ ESI ） with a positive-ion and multiple reaction monitoring mode was adopted. The precursor ion → product ion transitions m/z 316.2 → 110.3 for penehyclidine and m/z 256.2→167.2 for diphenhydramine （internal standard ）were monitored. Results： The plasma standard curve were linear in the range of 0.10-8.00 ng·mL^-1. The limit of quantification was 0.10 mg·mL-1. The plasma extraction recovery of penehyclidine was 85.8%-99.9%. Matrix effect were 79.7%-93.2%. The within-day and between-day RSDs were less than 11.1%. The main pharmacokinetic parameters of three test groups were as follows： Cmax were （ 2.65±1.06 ）, （ 4.88 ± 3.14 ）, and （ 5.93± 1.83 ） ng＂ mL^-1 , respectively; t1/2 were （ 29.35 ±13.56 ）, （ 25.22 ± 8.71 ）, and （ 26.41 ±6.81 ） h, respectively; AUC0-t were （ 71.81 ± 44.02 ）, （ 93.89 ± 65.14 ）, and （ 106.50 ± 53.01 ）h＂ ng· mL^-1 , respectively. Conclusion： The established method is proved to be suitable for determination of penehyclidine in human plasma. After oral administration of 0.4, 0.6, 0.8 mg penehyelidine hydroehloride table, the pharmacokineties behaviors exhibited good linear relationship.

关 键 词：戊乙奎醚 血药浓度 基质效应 固相萃取 药代动力学 方法验证 液相色谱串联质谱法 

分 类 号：R917[医药卫生—药物分析学]