摘要
目的建立测定人血浆中佐匹克隆浓度的HPLC法,比较国产与进口佐匹克隆片剂的药动学.方法以阿普唑仑作为内标物,采用ZorbaxRx-SIL(4.6 mm×150 mm,5 μm)正相色谱分析柱,流动相为乙腈-氯仿-正丁醇-水-三乙胺(420:40:23:10:0.24,V/V),流速0.8 mL·min-1;检测波长305 nm.8名健康男性志愿者随机、自身交叉口服国产和进口制剂7.5 mg.结果佐匹克隆血浆浓度线性范围为2.638～126.6 μg·L-1,回归方程c=0.044 67(Hs/Hi.s)-0.09479,r=0.999 2(P＜0.01),最低检测浓度2.638μg·L-1;日内、日间RSD均＜10%;方法回收率平均＞97%.结果显示,国产佐匹克隆片剂在体内符合一室开放线性模型,主要药动学参数tmax、 Cmax、 T1/2(ke)、AUC、CL及Vd值分别为(0.827 4±0.2893)h、(69.33±12.73)μg·L-1、(5.477±0.782 6)h、(593.90±139.50)μg·h·L-1、(13.16±2.677)L·h-1和(101.5±15.29)L;国产与进口制剂两者参数相比P＞0.05,采用方差双单侧t检验和(1-2α)置信区间法统计AUC、cmax,两制剂生物等效,相对生物利用度平均为(88.90±21.71)%.结论本法适合于人体佐匹克隆血药浓度测定,国产与进口佐匹克隆片剂生物等效.
A/M To develop a HPLC-UV method for determinating the concentration of zopiclone in human plasma and to compare the pharmacokinetics of zopiclone tablets of domestic vs imported. METHODS The analytic method was normal-phase HPLC with UV detection, using alprazolam as internal standard. The condition included ZorbaxRx-SIL （ 150 mm× 4.6 mm, 5 μm） column, the mobile phase consisted of acetonitrile/chloroform/n-butyl alcohol/water/triethy lamine （420：40：23： 10：0.24）, UV detector was set at 305 nm.A cross-over,self-control randomization design of trial was used with a oral dose of 7.5 mg zopiclone domestic or imported tablet in 8 male healthy volunteers. RESULTS The standard curves were linear over the range of 2.638 - 126.6 μg· L^-1 for zopiclone in plasma and the limit concentration was less than 2.638 μg· L^-1. The relative recovery averaged more than 97 %. The mean inter-and intra-assay coefficients of variation were less than 10%. The pharmacokinetic parameters of zopidone were evaluated by computing concentrationtime data of the subjects. CONCLUSION The method is stable and fitted with detection of zopiclone in human plasma. The domestic zopiclone tablet is equivalent to imported one.
出处
《中国临床药学杂志》
CAS
2005年第5期285-288,共4页
Chinese Journal of Clinical Pharmacy
