高效液相色谱法测定人体内氯苯那敏血药浓度及药动学

Determination of chlorpheniramine in plasma by HPLC and its pharmacokinetics

目的：建立高效液相色谱法测定人血浆中马来酸氯苯那敏药物浓度．并研究马来酸氯苯那敏健康人体药动学。方法：AgilentC1s柱（4．6mm×25（1mm，5μm），流动相为乙腈-（1．（125mol·L^-1。磷酸二氢铵溶液（pH3．5）（27：73），检测波长为200nm。10名健康志愿者单剂量口服8mg马来酸氯苯那敏片后，体内药时数据采用3tx）7程序统计方法处理。结果：本实验条件下，血浆样品中氯苯那敏无杂质干扰，线性关系良好，所得回归方程为：C=（1．3235A-（1．703．r=（1．9992，线性范围为（1．75～48．00μg·L^-1，本方法最低定量浓度为（1．75μ·L^-1，高、中、低3浓度日内和日间的RSD〈15％，提取回收率大于75％，满足生物样品的测定要求。马来酸氯苯那敏健康人体药动学参数Cmax为（16．4±8．9）μg·L^-1 tmax为（3．8±1．5）h．t1 2k为（13．1±2．3）h，V／F为（871．7±187．3）L，AUG11-t，为（181．5±52．3）μg·h·L^-1，AUG11-t为（2（18．2±6（1．1）μg·h·L^-1。结论：本法操作简便快速，定量准确可靠，适用于马来酸氯苯那敏片的人体药动学研究。

OBJECTIVE To establish an HPLC to determine the concentration in human plasma and study the pharmacokinetics of chlorpheniramine maleate in young healthy volunteers. METHODS The separation was performed on Agilent C18, （5 μm, 4. 6 mm× 251） mm）column. The mobile phase consisted of acetonitrile and 0. 025 mol. L^-1NH4 H2 PO4 water solution（pH 3.5）with the ratio of 27：73. The detection wavelength was at 200 nm. The healthy volunteers were given orally with a single dose of 8 mg chlorpheniramine maleate tablets and the data of concentrations-time in plasma were handled with 3P97 program. RESULTS The determination was not interfered under the optimal chromatographic conditions. The good linearity was obtained and the linear equation was C = 0. 323 5A - 0. 703 6 （r = 0. 999 2） in the range of 0. 75 - 48. 01） /,g. L ＇. The limit of quantitation was 0. 75μg.L^-1. The RSDs of within-day and between-day were less than 15 % （n = 5）, and extract recoveries were larger than 75%. The assay method was in conformity with the requirement of biological determination. The main pharmacokinetic parameters were as follows： The Cmax was （16.4± 8.9）μg. L^-1 , t was （3.8 ± 1.5）h, t1 2k was （13. 1 ± 2.3） h, V/F was （871.7± 187.3）L, AUG,, was （181.5 ± 52.3） μg. h. L^-1, AUG11-∞ was （208.2 ± 60. 1 ） /,g. h. L^-1 , respectively. CONCLUSION The assay method appeared to be simple, quick, accurate, reliable and suitable for the pharmacokinetic study of chlorpheniramine maleate.