醋酸泼尼松和泼尼松在Beagle犬体内的生物利用度比较  

Comparison of pharmacokinetics and bioavailability of prednisone acetate and prednisone in Beagle dogs

作　　者：吴彩凤 朱云婷 张逸凡 钟大放[1,2] WU Cai-feng;ZHU Yun-ting;ZHANG Yi-fan;ZHONG Da-fang(College of Pharmaceutical Science,Zhejiang University of Technology,Hangzhou 310014,China;Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China)

机构地区：[1]浙江工业大学药学院,浙江杭州310014 [2]中国科学院上海药物研究所,上海201203

出　　处：《药学学报》2020年第6期1251-1256,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81521005,81703602)。

摘　　要：本文通过Beagle犬双周期随机交叉灌胃给予醋酸泼尼松(2.0 mg·kg^-1)和泼尼松(1.8 mg·kg^-1),建立液相色谱-串联质谱(LC-MS/MS)法同时测定Beagle犬血浆中的醋酸泼尼松、泼尼松及活性代谢物泼尼松龙的浓度,比较醋酸泼尼松和泼尼松的生物利用度及药代动力学。本实验方案经中国科学院上海药物研究所实验动物伦理委员会批准。采用地塞米松作为内标,血浆样品以乙腈沉淀蛋白后,经HSS T3(50 mm×2.1 mm,1.8μm)色谱柱分离,以甲醇-0.1%甲酸的5 mmol·L^-1醋酸铵水溶液作为流动相进行梯度洗脱。采用电喷雾离子源,以多反应监测正离子模式检测。用于定量分析的醋酸泼尼松、泼尼松及泼尼松龙的离子对分别为m/z 401.2→295.2、m/z 359.2→313.2和m/z 361.2→325.1,内标的离子对为m/z 393.2→373.0。结果表明,醋酸泼尼松在血浆中的含量低于分析方法的定量下限1.0 ng·mL^-1,说明醋酸泼尼松在体内吸收过程中快速水解;醋酸泼尼松给药后,泼尼松Cmax为(25.1±3.61)ng·mL^-1AUC0-t为(115±27.2)h·ng·mL^-1,泼尼松龙Cmax为(207±38.5)ng·mL^-1,AUC0-t为(760±218)h·ng·mL^-1;泼尼松给药后,泼尼松Cmax为(67.9±22.6)ng·mL^-1,AUC0-t为(160±19.3)h·ng·mL^-1,泼尼松龙Cmax为(582±81.4)ng·mL^-1AUC0-t为(1310±140)h·ng·mL^-1。Beagle犬给予泼尼松后,泼尼松Cmax和AUC0-t分别约为给予醋酸泼尼松的2.6倍和1.4倍;泼尼松龙Cmax和AUC0-t分别约为给予醋酸泼尼松的2.8倍和1.8倍。通过计算泼尼松龙AUC0-t的比值,得到醋酸泼尼松相对于泼尼松的生物利用度仅为57.1%。An LC-MS/MS method was developed for the simultaneous determination prednisone acetate prednisone and active metabolite prednisolone in dog plasma,and applied to a bioavailability and pharmacokinetics study of oral dose of prednisone acetate(2.0 mg·kg^-1)and prednisone(1.8 mg·kg^-1)given to Beagle dogs in a randomized,two-way crossover study.This experiment scheme was approved by the Experimental Animal Ethics Committee of Shanghai Institute of Medicine,Chinese Academy of Sciences.Dexamethason was used as internal standard.After extraction from the plasma by protein precipitation,the analytes and internal standard were separated on an HSS T3(50 mm×2.1 mm,1.8μm)column using a gradient elution procedure.The mobile phase consisted of methanol and 5 mmol·L-1ammonium acetate aqueous solution(0.1%formic acid).Positive electrospray ionization was performed using multiple reaction monitoring(MRM)with transitions of m/z 401.2→295.2 for prednisone acetate,m/z 359.2→313.2 for prednisone,m/z 361.2→325.1 for prednisolone,m/z 393.2→373.0 for dexamethason After prednisone acetate was administered,the Cmaxof prednisone was(25.1±3.61)ng·mL^-1 and AUC0-twas(115±27.2)h·ng·mL^-1,while the Cmaxof prednisolone was(207±38.5)ng·mL^-1 and AUC0-twas(760±218)h·ng·mL^-1 After prednisone was administered,the Cmaxof prednisone was(67.9±22.6)ng·mL^-1 and AUC0-twas(160±19.3)h·ng·mL^-1,while the Cmaxof prednisolone was(582±81.4)ng·mL^-1 and AUC0-twas(1310±140)h·ng·mL^-1 The relative bioavailability of prednisone acetate to prednisone was only 57.1%.

关 键 词：液相色谱-串联质谱 醋酸泼尼松 泼尼松 泼尼松龙 生物利用度 

分 类 号：R917[医药卫生—药物分析学]