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Establishment of high sensitive analysis for psychotropic drugs using in付ube SPME/LC/MS

管内 SPME/LC/MS 精神药物高灵敏分析方法的建立

基本信息

批准号：
15590589
负责人：
KUMAZAWA Takeshi
金额：
$ 2.3万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

In the present study, we established a procedure for the determination of psychotropic drugs, phenothiazines, butyrophenones and benzodiazepines, in human samples by in-tube solid-phase microextraction (SPME)/high-performance liquid chromatography (LC)/mass spectrometry (MS).In-tube SPME was achieved with SupelcoWaxl0 capillary column (60cm, 0.32mm id., 0.25μm film thickness) for phenothiazines and butyrophenones, and Supelco-Qplot capillary capillary column (50cm, 0.32mm id, 0.25 μm film thickness) for benzodiazepines. The optimum extraction conditions for phenothiazines and butyrophenones from serum and urine samples were 15-20 draw/eject cycles of 30-35 μl of the sample containing Tris-HC1 (pH 8) at a flow rate of 0.1 ml/min. The chromatographic separation of phenothiazines and butyrophenones was carried out with a Capcell Pak C_<18> column (150mm, 2mm i.d.) with 10mM ammonium formate/0.1% formate/acetonitrile as a mobile phase at a flow rate of 0.2ml/min. For benzodiazepines, the o … More ptimum extraction conditions from serum and urine samples were 35 draw/eject cycles of 35 μl of the sample containing Tris-HC1 (pH 8.5) at a flow rate of 0.1 ml/min. The chromatographic separation of benzodiazepines was carried out with a Symmetry Shield RP_<18> column (150mm, 2.1mm i.d.) with 50mM ammonium formate/0.1% formic acid/methanol as a mobile phase at a flow rate of 0.2ml/min. LC/MS with electrospray ionization as interface and positive mode were used for detection of all drugs. In the present method, LC/tandem MS (MS/MS) showed much higher sensitivity than LC/MS. The detection limits of all drugs were 20ng-2 μg/ml for serum and 0.5-1 ng/ml for urine using LC/MS/MS with selected reaction monitoring (SRM). In addition to the spiked human body fluids, the method was applied to serum sample after oral administration of phenothiazine (perazine) by a male volunteer; the drug could be isolated from serum sample by in-tube SPME and sensitively quantified by SRM.The present in-tube SPME/LC/MS method can be recommended for use in therapeutic monitoring, clinical toxicology and forensic toxicology. Less

本研究建立了管内固相微萃取(SPME)/高效液相色谱(LC)/质谱（MS）法测定人体样品中精神药物吩噻嗪类、丁苯酮类和苯二氮卓类的方法。采用supelcowax10毛细管柱（60cm, 0.32mm）进行管内SPME测定。采用Supelco-Qplot毛细管柱（50cm, 0.32mm id， 0.25μm膜厚）测定苯二氮卓类药物。从血清和尿液中提取吩噻嗪类和丁苯酮类药物的最佳工艺条件为：抽吸15 ~ 20次，萃取量为30 ~ 35 μl，流速为0.1 ml/min。色谱分离采用Capcell Pak C_<18>色谱柱（150mm，直径2mm），流动相为10mM甲酸铵/0.1%甲酸酯/乙腈，流速为0.2ml/min。血清和尿液中苯二氮卓类药物的最佳提取条件为：提取35 μl含Tris-HC1 （pH 8.5）的样品，流速为0.1 ml/min，抽吸/排出35次。采用对称屏蔽柱（RP_<18>, 150mm， 2.1mm流速），流动相为50mM甲酸铵/0.1%甲酸/甲醇，流速为0.2ml/min，对苯二氮卓类药物进行色谱分离。采用电喷雾电离为界面，正模式的LC/MS对所有药物进行检测。在本方法中，LC/串联质谱（MS/MS）的灵敏度明显高于LC/MS。采用选择性反应监测（SRM）的LC/MS/MS方法，所有药物的检出限分别为血清20 ~ 2 μg/ml和尿液0.5 ~ 1 ng/ml。除加标的体液外，该方法还应用于男性志愿者口服吩噻嗪（perazine）后的血清样本；用管内SPME法可从血清样品中分离出该药，用SRM法可灵敏定量。本方法可推荐用于治疗监测、临床毒理学和法医毒理学。少