盐酸氯卡色林渗透泵控释片在Beagle犬中的血药浓度测定方法的建立及其药代动力学研究  

Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study

作　　者：张苗苗 蒋成君 王重阳 葛廷雨 宋琦琪 李真宝 汪电雷 ZHANG Miao-miao;JIANG Cheng-jun;WANG Chong-yang;GE Ting-yu;SONG Qi-qi;LI Zhen-bao;WANG Dian-lei(College of Pharmacy,Anhui University of Chinese Medicine,Hefei 230011,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230011

出　　处：《中国药理学通报》2023年第5期993-997,共5页Chinese Pharmacological Bulletin

基　　金：安徽省高校自然科学基金项目资助(No KJ2019ZD33)。

摘　　要：目的建立UPLC-MS/MS法测定Beagle犬血浆中盐酸氯卡色林的浓度,并用于盐酸氯卡色林渗透泵控释片在Beagle犬体内的药代动力学研究。方法采用随机交叉法设计实验,以卡马西平为内标,利用乙腈沉淀血浆中的蛋白进行血浆样品处理。色谱柱为Phenomenex Polar C_(18)柱(100 mm×2.1 mm,3μm),流动相是乙腈-水(含10 mmol·L^(-1)醋酸铵和0.1%甲酸)(40∶60)。采用电喷雾离子源,正离子、多反应监测方式进行定量,盐酸氯卡色林和卡马西平的检测离子对分别为m/z 196.2→129.1、m/z 237→194.1。结果盐酸氯卡色林的线性范围为1~500μg·L^(-1)(r=0.9992),提取回收率为87.70%~89.10%,批内、批间的精密度RSD≤9.7%,准确度、基质效应均符合要求,盐酸氯卡色林分别在-20℃冰箱保存45 d、反复冻融3次、室温放置24 h、以及处理后的样品在自动进样器中放置6 h的稳定性均良好。控释片和速释片的药动学参数T_(max)分别为(8.0±1.27)h和(1.0±0.13)h,C_(max)分别为(70.56±3.73)μg·L^(-1)和(176.33±16.73)μg·L^(-1),AUC_(0-t)分别为(966.33±37.56)μg·h·L^(-1)和(973.05±69.09)μg·h·L^(-1)。结论建立的UPLC-MS/MS方法,可用于Beagle犬血浆中盐酸氯卡色林药代动力学研究,渗透泵控释片具有缓释作用。Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma,and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride.Methods A randomized crossover design was used,carbamazepine as the internal standard(IS),and plasma protein precipitation with acetonitrile.The chromatographic was Phenomenex Polar C 18 column(100 mm×2.1 mm,3μm),and acetonitrile-water(containing 10 mmol·L^(-1)ammonium acetate and 0.1%formic acid)(40∶60,V/V)was mobile phase.Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride.The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine,respectively.Results The linear range was 1 to 500μg·L^(-1)(r=0.9992),the extraction recovery rate ranged from 87.70%to 89.70%,the precision RSD was 9.7%.The accuracy and matrix effect met the requirements,and the stability of lorcaserin hydrochloride was good in-20℃refrigerator for 45 d,repeated freezing and thawing for three times,placed at room temperature for 24 h,and the disposed samples placed in automatsampler for 6 h were stable.The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:T_(max)was(8.00±1.27)h and(1.00±0.13)h,C_(max)was(70.56±3.73)μg·L^(-1)and(176.33±16.73)μg·L^(-1),and AUC_(0-t)was(966.33±7.56)μg·h·L^(-1)and(973.05±69.09)μg·h·L^(-1),respectively.Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs,and osmotic pump controlled-release tablets has sustained release effect.

关 键 词：盐酸氯卡色林 UPLC-MS/MS 药代动力学 渗透泵 控释片 BEAGLE犬 

分 类 号：R-332[医药卫生] R916.4R944.9R969.1R977.9