HPLC法检测盐酸戊乙奎醚R型异构体经小鼠尿排泄的方法学研究  

Method studies on HPLC determination of R-isomers of penehyclidine hydrochloride in urine excretion in mice

作　　者：薛明[1] 阮金秀[2] 张振清[2] 袁淑兰[2] 吴波[2] 李宇航[1] 

机构地区：[1]首都医科大学药物研究所药理教研室,北京100054 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国临床药理学与治疗学》2003年第4期425-427,共3页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的 :建立HPLC测定方法研究R型盐酸戊乙奎醚光学异构体在小鼠体内的排泄。方法 :采用新建立的正相HPLC法 ,尿样经提取处理后 ,选用SpherisorbSiO2 色谱柱 ,以甲醇 二氯甲烷 氨水 (8 2 0 .1)为流动相 ,流速 0 .8ml·min-1,检测波长2 5 4nm ,进样量 2 0 μl。结果 :在 0 .5～ 10 0mg·L-1浓度范围内 ,R异构体峰面积与浓度呈良好的线性关系 (r分别为 0 .9994与 0 .9997)。两R型异构体的平均回收率均大于 85 % ,日内和日间RSD均小于13%。小鼠肌注给药后不同时间内 ,R型异构体在尿中的比值 (R 1 R 2 )存在显著差异 (P <0 .0 5 )。4 8h内R型异构体在尿中的排泄量明显不同。结论 :本法简单方便 ,可用于R型异构体在小鼠体内立体选择性排泄研究。AIM: To study a method of HPLC determination of R-isomers of penehyclidine hydrochloride (R-PHC) in mouse urine excretion. METHODS: Urine samples were collected and prepared after i.m. a single dose 30 μg of R-PHC in mice. The HPLC system consisted of Spherisorb SiO_2 column, methanol-dichloromethane-ammonia liquor (82 0.1 ) as mobile phase with 254 nm, flow rate: 0.8 ml·min -1 , and injection volume of 20 μl. RESULTS: The linear range was 0.5 -100 mg·L -1 (r= 0.9994 and 0.9997 , respectively), and the average recovery was more than 85%. The RSD of intra-day and inter-day assays of two isomers were all less than 13%. The limit of detection proved to be 0.1 μg·ml -1 . The ratio of R-1/R-2 in urine changed within the time after dosing. The cumulative excretion of the two optical isomers had distinguished differences (P< 0.05 )in urine. CONCLUSION: This HPLC method is simple and convenient, and able to investigate the stereo-selective excretion of R-PHC isomers in urine.

关 键 词：高压液相色谱法 盐酸戊乙奎醚 光学异构体 排泄 

分 类 号：R965[医药卫生—药理学] R965.2[医药卫生—药学]