Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130021, PR China.
J Pharm Biomed Anal. 2010 Feb 5;51(3):716-22. doi: 10.1016/j.jpba.2009.10.009. Epub 2009 Oct 14.
A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous quantitation of paracetamol, caffeine, pseudoephedrine, chlorpheniramine and cloperastine in human plasma has been developed and validated. After sample preparation by liquid-liquid extraction, the analytes and internal standard (diphenhydramine) were analyzed by reversed-phase HPLC on a Venusil Mp-C(18) column (50mmx4.6mm, 5microm) using formic acid:10mM ammonium acetate:methanol (1:40:60, v/v/v) as mobile phase in a run time of 2.6min. Detection was carried out by electrospray positive ionization mass spectrometry in the multiple-reaction monitoring mode. The method was linear for all analytes over the following concentration (ng/ml) ranges: paracetamol 5.0-2000; caffeine 10-4000; pseudoephedrine 0.25-100; chlorpheniramine 0.05-20; cloperastine 0.10-40. Intra- and inter-day precisions (as relative standard deviation) were all < or =11.3% with accuracy (as relative error) of +/-5.0%. The method was successfully applied to a study of the pharmacokinetics of the five analytes after administration of a combination oral dose to healthy Chinese volunteers.
建立并验证了一种基于液相色谱-串联质谱（LC-MS/MS）的快速、灵敏的方法，用于同时定量测定人血浆中的扑热息痛、咖啡因、伪麻黄碱、氯苯那敏和克仑特罗。经过液液萃取样品制备后，采用反相 HPLC 法，在 Venusil Mp-C(18)柱（50mmx4.6mm，5μm）上，以甲酸：10mM 乙酸铵：甲醇（1:40:60，v/v/v）为流动相，运行时间为 2.6min，以内标（苯海拉明）为内标，对分析物和内标（苯海拉明）进行分析。采用电喷雾正离子化质谱，在多重反应监测模式下进行检测。该方法在以下浓度（ng/ml）范围内对所有分析物均呈线性：扑热息痛 5.0-2000；咖啡因 10-4000；伪麻黄碱 0.25-100；氯苯那敏 0.05-20；克仑特罗 0.10-40。日内和日间精密度（以相对标准偏差表示）均<或=11.3%，准确度（以相对误差表示）为+/-5.0%。该方法成功地应用于研究健康中国志愿者口服联合剂量后 5 种分析物的药代动力学。
