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

关键词:  氯哌丁  氯苯那敏  伪麻黄碱  液相色谱-质谱联用  药动学

Key words:  cloperastine  chlorpheniramine  psedoephedrine  LC-MS  pharmacokinetics

摘要:

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-pack ODS柱（150 mm×2.0 mm，5 μm）；流动相为含0.5‰冰醋酸和0.5 mmol·L-1醋酸铵的水溶液及甲醇；检测离子为m/z 330.1（氯哌丁）、m/z 275.0（氯苯那敏）、m/z 166.0 （伪麻黄碱）及m/z 256.15（内标）；裂解电压为25 V。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6.25～400.0 ng·mL-1；最低可定量浓度分别为0.5，6.25和0.2 ng·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。

Abstract:

OBJECTIVE To establish an LC-MS for 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). LC-MS was performed in the selectedion 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 RSD 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.