LC-MS同时测定人血浆中氯哌丁、氯苯那敏和伪麻黄碱

Simultaneous Determination of Cloperastine,Chlorpheniramine and Psedoephedrine Concentrations in Human Plasma by LC-MS

目的建立一种同时测定人血浆中氯哌丁、氯苯那敏和伪麻黄碱的LC-MS,并用于含上述组分的复方酚咖伪麻胶囊人体药动学研究。方法以苯海拉明为内标,血样经乙酸乙酯提取后,采用LC-MS进行测定。色谱柱为Shim-packODS柱(150mm×2.0mm,5μm);流动相为含0.5‰冰醋酸和0.5mmol.L-1醋酸铵的水溶液及甲醇;检测离子为m/z330.1(氯哌丁)、m/z275.0(氯苯那敏)、m/z166.0(伪麻黄碱)及m/z256.15(内标);裂解电压为25V。结果氯哌丁、氯苯那敏和伪麻黄碱的线性范围分别为0.5～50.0,0.2～25.0和6.25～400.0ng.mL-1;最低可定量浓度分别为0.5,6.25和0.2ng.mL-1;日内、日间RSD小于10%,方法回收率均大于85%。结论该方法简便,快速,重复性好,灵敏度高,可用于含氯哌丁、伪麻黄碱和氯苯那敏的复方制剂临床药动学研究。

OBJECTIVE To establish an LC-MS tot simultaneous determine the concentration of cloperastine,chlorpheniramine and psedoephedrine in human plasma and to apply this method to the pharmacokinetic and bioavailability study of above components after oral administration of a compound preparation. METHODS Using diphenhydramin hydrochloric as internal standard, plasma was extracted with ethyl acetate and separated by a C18 column with the mobile phase of methanol-water （ including 0.5‰ acetic acid and 0.5 mmol·L^-1 ammoniium acetate）. I,C-MS was performed in the selected ion monitoring mode using target ions was at m/z 330.1 for cloperastine, m/z 275. 0 for chlorpheniramine, m/z 166. 0 for psedoephedrine and m/z 256. 15 for diphenhydramin hydrochloric（ IS ）. The fragmentor voltage was 25 V. RESULTS The linear range of cloperastine, chlorpheniramine and psedoephedrine in human plasma were 0.5 - 50.0,0.2 - 25.0 and 6.25 - 400.0 ng·mL^-1, respectively. The limit of determination were 0.5, 6.25 and 0.2 ng·mL^-1 , respectively. The recoveries of methodology were all more than 85%. The inter-day and intra-day RSI） were all less then 10%. CONCLUSION This method has good sensitivity and precision. It is shown to be suitable for pharmacokinetics studies of different compound preparations containing low dosage of cloperastine,chlorpheniramine,psedoephedrine.