隐形盐酸阿霉素脂质体注射液药代动力学的实验研究  

Experimental study on pharmacokinetics of stealth liposomal doxorubicin hydrochloride

作　　者：唐利安[1] 陈知航[1] 侯禹男[1] 单成启[1] 刘萍[1] 程远国[1] 王忠伟 

机构地区：[1]军事医学科学院微生物流行病研究所药学研究室,北京100071 [2]通化同剂医院,吉林通化134000

出　　处：《中国临床药理学杂志》2006年第4期292-294,共3页The Chinese Journal of Clinical Pharmacology

摘　　要：目的建立LC-MS/MS法,测定Beagle犬血浆中盐酸阿霉素脂质体注射液浓度并研究其药代动力学.方法Beagle犬6只,静脉滴注隐形盐酸阿霉素脂质体1 mg·kg^-1,用液相色谱-串联质谱法测定盐酸阿霉素血药浓度,并计算其药代动力学参数.结果阿霉素线性范围为37.5～10 000ng mL^-1,定量下限为37.5ng mL^-1;日内、日间均CV＜9.0%.主要药代动力学参数：t1/2为（24.7±0.7）h,Cmax为（21.7±0.9）μg·mL^-1,AUC0-120h,AUC0-∞和AUC120-∞分别为（698.1±100.1）,（716.4±102.1）,（18.2±2.8）μg·h·mL^-1,MRT为（34.1±2.0）h,CL为（1.42±0.20）mL·（h·kg）^-1,Vss为（48.4±6.5）mL·kg^-1.结论该法操作简便、快速、灵敏,可用于测定犬血浆中阿霉素浓度和药代动力学研究.Objective To establish a sensitive and specific LC -MS/MS method for determination of stealth liposomal doxorubicin hydrochloride （SLDH） in beagle dogs plasma. Methods Six Beagle dogs were given in travenously SLDH 1 mg · kg^-1. The doxorubicin concentration was determined by liquid chromatography- tandem mass spectroscopy （LC -MS/ MS）. Results The linearity ranged from 37.5 to 10 000 ng·mL^-1 （γ= 0. 9987）. The detectction of SLDH was 37.5 ng·mL^-1. The CV（ % ） within day and between day was less than 9 %. The main pharmacokinetic parameters were as follows：t1/2 was （24.7 ±0.7） h,Cmax was （21.7 ± 0.9）μg·mL^-1, AUC0-120h AUC0-∞和AUC120-∞ were （698. 1 ± 100. 1） ,（716.4 ± 102.1）,（18.2 ± 2.8）μg· h· mL^-1 respectivey, MRT was （34.1 ± 2.0） h, CLwas （1.42 ± 0.20） mL · （h · kg）^-1,and Vss was （48.4 ± 6.5） mL · kg^-1. Conclusion The precision,accuracy and recovery method were found to be adequate for pharmacokinetic studies.

关 键 词：隐形阿霉素脂质体 液相色谱-串联质谱法 药代动力学 

分 类 号：R969.1[医药卫生—药理学] R984.3[医药卫生—药学]