摘要
采用高效液相色谱法测定去甲地西泮（去甲安定）及其代谢产物奥沙西泮。以ＲＰ－Ｃ１８为固定相，乙腈—０．０１ｍｏｌ·Ｌ－１醋酸钠（ｐＨ３．８，３３．３：６６．６）为流动相，地西泮为内标物，紫外波长２４０ｎｍ处定量测定。去甲地西泮、奥沙西泮和内标物的保留时间分别为２．８ｍｉｎ，４．８５ｍｉｎ和８．５ｍｉｎ；绝对回收率分别为７４％，８６％和８６％。奥沙西泮在３５．３～２２６０ｎｇ·ｍｌ－１，去甲地西泮在２０～２５６０ｎｇ·ｍｌ－１血浆浓度范围内线性关系良好，ｒ＝０．９９９７和ｒ＝０．９９９８。二药的最低检测浓度分别为１０ｎｇ·ｍｌ、和７ｎｇ·ｍｌ－１；日内和日间相对标准偏差（ＲＳＤ）均分别小于６％和１０％（ｎ＝５）。多种常用药物对样品的色谱峰无干扰。并用此法研究了大鼠单次口服去甲地西泮的药代动力学。
A simple rapid and sensitive HPLC method for
simulaneous determination of N-demethyldiazepam and its metabolite
oxazepam i n both human and rat plasma was described.Areversed phase
C18 column equipped with a 240 nm detector were selected.
Diazepam was used as internal standard.The mobile phase consisted
of acetonitrile 0. 01 mol·L-1 sodium acetate buffer(pH3.8,33.3 :
66.6v/v). The retention time for N-demethyldiazepm, oxazepam and
internalstandard were 4. 85 min,2. 8 min and 8. 5 min, reapectively.
The lower detection limits foroxazepm and N- demethyldiazepam were
10 ng ml-1 and 7 ng· ml-1 ,respectively. The precisions(RSD%,n=5 )
of within-day and day-to-day were less than 6%and 1 0%and their
absoluterecoveries were 74%and 86%, respectively. The pharmacokinetic
characteristics of N-demethyldiazepam in Sprague-Dawley rats after a
single oral dose of 2.5mg· kg-1 was investigated by thismethod, The
concentration-time curve was fitted to a two-compartment open
model.Its main pharma-cokinetic parameters were:Tmax=0.
24h,Cmax=1211.78ng·ml-1,T β=2.84h, AUC=1264ng·ml-1·h-1.
出处
《药学学报》
CAS
CSCD
北大核心
1995年第9期655-661,共7页
Acta Pharmaceutica Sinica
基金
博士点基金
