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夸西泮舌下给药后夸西泮及其代谢产物的液相色谱分析及药代动力学

Liquid chromatographic assay and pharmacokinetics of quazepam and its metabolites following sublingual administration of quazepam.

作者信息

Gupta S K, Ellinwood E H

机构信息

Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710.

出版信息

Pharm Res. 1988 Jun;5(6):365-8. doi: 10.1023/a:1015907611170.

DOI:10.1023/a:1015907611170
PMID:3244647
Abstract

A reverse-phase liquid chromatographic method is described for simultaneous quantification of quazepam, and two of its metabolites, 2-oxoquazepam and N-desaklyl-2-oxoquazepam. The method uses a solid-phase extraction procedure to prepare plasma samples. After extraction, the methanolic extract is evaporated; the residue is then reconstituted in a small volume of mobile phase and chromatographed. The total chromatography time for a single sample is about 20 min. A sensitivity of 1 ng/ml for quazepam and its metabolites is attained when 1 ml of plasma is extracted. Analytical recovery of quazepam and its metabolites added to plasma ranged from 87 to 96%. The maximum within-day and day-to-day coefficients of variation for each compound at concentrations of 20 and 60 ng/ml were 7.6 and 11.2%, respectively. The method was applied to sublingual pharmacokinetic studies of quazepam in healthy volunteers.

摘要

描述了一种反相液相色谱法,用于同时定量地西泮及其两种代谢物,即2-氧代地西泮和N-去烷基-2-氧代地西泮。该方法采用固相萃取程序制备血浆样品。萃取后,将甲醇提取物蒸发;然后将残留物用少量流动相复溶并进行色谱分析。单个样品的总色谱分析时间约为20分钟。当提取1 ml血浆时,地西泮及其代谢物的灵敏度达到1 ng/ml。添加到血浆中的地西泮及其代谢物的分析回收率在87%至96%之间。每种化合物在浓度为20和60 ng/ml时,日内和日间最大变异系数分别为7.6%和11.2%。该方法应用于健康志愿者中地西泮的舌下给药药代动力学研究。

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本文引用的文献

1
Effect of sleep on quazepam kinetics.睡眠对夸西泮动力学的影响。
Clin Pharmacol Ther. 1984 Jul;36(1):99-104. doi: 10.1038/clpt.1984.146.
2
Gas chromatographic determination of quazepam and two major metabolites in human plasma.气相色谱法测定人血浆中夸西泮及其两种主要代谢物
J Pharm Sci. 1984 Apr;73(4):516-9. doi: 10.1002/jps.2600730421.
3
Plasma quantification of quazepam and its 2-oxo and N-desmethyl metabolites by capillary gas chromatography.采用毛细管气相色谱法对夸西泮及其2-氧代和N-去甲基代谢物进行血浆定量分析。
J Chromatogr. 1986 May 28;378(1):137-45. doi: 10.1016/s0378-4347(00)80706-9.
4
Disposition and metabolic fate of 14C-quazepam in man.14C-夸西泮在人体内的处置及代谢转归
Drug Metab Dispos. 1985 Jan-Feb;13(1):25-9.
5
ESTRIP, a BASIC computer program for obtaining initial polyexponential parameter estimates.ESTRIP,一个用于获取初始多指数参数估计值的BASIC计算机程序。
J Pharm Sci. 1978 Dec;67(12):1687-91. doi: 10.1002/jps.2600671214.