新西兰兔血浆中格拉司琼浓度的UFLC-MS/MS法测定及其经皮给药贴片的药动学研究  

Determination of concentration of granisetron in New Zealand rabbit plasma by UFLCMS/MS and its application to pharmacokinetic study after transdermal administration

作　　者：武余波[1] 罗华菲[1] 朱慧勇[1] 陈纯[1] 沈承武[2] 

机构地区：[1]中国医药工业研究总院药物制剂国家工程研究中心,上海201203 [2]山东大学附属省立医院,济南250021

出　　处：《世界临床药物》2014年第3期145-150,共6页World Clinical Drug

基　　金：国家"重大新药创制"科技重大专项(2012ZX09304004)

摘　　要：目的建立UFLC-MS／MS法测定格拉司琼的血药浓度，研究自制盐酸格拉司琼透皮贴片和Sancuso贴片在新西兰兔体内的药动学行为。方法采用平行设计，12只新西兰兔按随机区组设计分为给药组和对照组，每组6只，分别给予自制贴片和Sancuso贴片，采用经验证的UFLC—MS／MS法测定兔血浆中格拉司琼浓度。使用DAS2．1．1软件计算药动学参数。结果格拉司琼在1．0～500ng／ml范围内线性关系良好，方法回收率为92．5％～101．4％，日内、日间精密度的RSD均小于5％。新西兰兔经皮给予自制贴片和Sancuso贴片的主要药动学参数AUC（0-1]为（2106±337．0）与（2402±557．7）pg／L．h、AUC（0-∞））为（2107±336．8）与（2404±558．7）μg／L·h、Cmax为（63．03±17．53）与（82.32±34．76）μg／L、Tmax为（3．7±2．3）与（4．8±3．2）h、正。为（2．4±1．5）与（3．5±2．5）h。结论本方法高效、快速、灵敏、准确、专属性强，适用于格拉司琼血药浓度的监测。本研究结果显示，格拉司琼在兔体内的吸收和消除速度快，且两种贴剂Cmax、AUC（0-1）和AUC（0-∞）在相同给药周期下的组间差异具有统计学意义。Objective To develop an UFLC-MS/MS method for the determination of granisetron concentration in New Zealand rabbits plasma and to investigate the pharmacokinetics of self-made granisetron hydrochloride transdermal patches and Sancuso patches. Methods Using parallel design, a total of 12 New Zealand rabbits were randomly divided into the drug-exposed group and the control group with 6 rabbits in each group, which were given self-made patches and Sancuso＇s patches respectively. The plasma concentration of granisetron was determained by a validated UFLC-MS/MS method. The pharmacokinetic parameters were calculated by DAS 2.1.1. Results The calibration curve of granisetron was linear within the concentration range of 1.0-500 ng/ml. The method recoveries were within 92.5%- 101.4%. The RSDs of intra- and inter-day presicion were less than 5%. The mean pharmacokinetic parameters were as follows： AUC （0-t） （2106 ± 337.0） and （2402±557.7） μg/L.h, AUC（0-∞） （2107±336.8） and （2404±558.7）μg/-L.h, Cmax （63.03±17.53） and （82.32±34.76） μg/L, Tax （3.7±2.3） and （4.8±3.2） h, T1/2 （2.4±1.5） and （3.5±2.5） h, respectively for self-made patches and Sancuso＇s patches. Conclusion The UFLC-MS/ms method is effective, rapid, sensitive, accurate, specific and suitable for granisetron therapeutic drug monitoring. The pharmacokinetics results indicated that self-made patches and Sancuso＇s patches were different significantly over the same administration cycle.

关 键 词：格拉司琼 超高效液相色谱 串联质谱法 液-液萃取 经皮 贴片 药物动力学 

分 类 号：R975.4[医药卫生—药品] R965[医药卫生—药学]