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High-Performance Liquid Chromatography/Mass Spectrometry of Psychotropic Drugs

精神药物的高效液相色谱/质谱分析

基本信息

批准号：
06670469
负责人：
SATO Keizo
金额：
$ 1.34万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

We analyzed three representative psychotropic drugs, benzodiazepines, phenothiazines and butyrophenones, by our recently established system of capillary high-performance liquid chromatography (HPLC) /fast atom bombardment (FAB) -mass spectrometry (MS). The authentic compounds of 27 benzodiazepines, 17 phenothiazines and 6 butyrophenones were analyzed by the system. Quasi-molucular peaks along with adequate fragment peaks were detected in the positive mode for most compounds under investigation with the detection limit of less than 10ng on columun. Sensitivity in the nagative mode with respect to its mass spectral measurement was two order of magnitude lower than that in the positive mode.The extraction of the drugs from human blood or urine was studied using various solid-phase extraction cartridges. In general, C_<18> cartridges were effective for the isolation of benzodiazepines, C_2 cartridges for that of phenothiazines or butyrophenones. With this isolation procedure and the capillary HPLC/FAB-MS in the positive mode, some representative benzodiazepines or phenothiazines together with their metabolites could be identified in human sera after oral administration of them.We established a method for quantitative analysis of the concentration of midazolam, one of representative benzodiazepines, in serum by selected ion-monitoring (SIM) of FAB-MS, using deuterium-labeled midazolam as an internal standard. The calibration graph was linear for concentrations between 2ng/ml and 200ng/ml, and reproducibility was good. The capillary HPLC/FAB-MS was semi-quantitative for all compounds under investigation. However, we feel that accurate quantitation can be made by SIM of FAB-MS with a suitable isotopic internal standard. We also devised a simple method for quantitation of some benzodiazepines in human serum by UV monitoring of the capillary HPLC.These analytical methods devised in this study would seen to be useful in clinical pharmacology as well as in forensic toxicology.

采用毛细管高效液相色谱（HPLC）/快原子轰击（FAB）-质谱（MS）联用技术，对苯二氮卓类、吩噻嗪类和丁酰苯类3种典型精神药物进行了分析。该系统分析了27种苯二氮卓类、17种吩噻嗪类和6种丁酰苯类的真实化合物。大多数化合物在正离子模式下均检出准分子峰沿着有足够的碎片峰，柱上检出限小于10 ng。负离子模式的质谱测量灵敏度比正离子模式低两个数量级。C_2<18>柱对苯并二氮杂卓类药物的分离效果较好，对吩噻嗪类和丁酰苯类药物的分离效果较好。采用该分离方法和正离子模式下的毛细管高效液相色谱-快速原子吸收-质谱联用技术（FAB-MS），可在人体口服苯二氮卓类药物或吩噻嗪类药物后的血清中同时检测出其代谢产物，并建立了FAB-MS选择离子监测（SIM）法定量分析血清中咪唑安定的方法。使用氘标记的咪达唑仑作为内标。线性范围为2 ~ 200 ng/ml，重现性好。毛细管HPLC/FAB-MS对所有研究化合物均为半定量。然而，我们认为，准确的定量可以通过SIM的FAB-MS与合适的同位素内标。本文还建立了一种简便的人血清中苯二氮卓类药物的毛细管高效液相色谱紫外检测方法，为临床药理学和法医毒理学研究提供了一种新的分析方法。