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A developmental model of the computer-assisted HPLC multiwavelength UV detection system for simultaneous toxicological drug analysis

药物毒理学同步分析计算机辅助高效液相色谱多波长紫外检测系统的开发模型

基本信息

批准号：
61870114
负责人：
WATANABE Tokinori
金额：
$ 3.2万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

A new emergency drug screening system for separation and identification of the toxic drugs, "MULTI-HPLC" is presented. The HPLC system used comprised a Model 880-PU pump and Multi-320 multichannel UV detector (Jasco). The column was a Jasco FineSil C18S(250mmx4.6mmI.D.) set at 50゜C. The mobile phases were mixtures of 10mM perchloric acid, 10mM sodium perchlorate and acetonitrile (CH_3 CN) and flow-rate was 1ml/min.Sixty-five toxic drugs, frequently seen in drug poisoning cased in Japan, were selected as the reference drugs. According to the pharmacological effect, they were classified as antipsychoactive, antianxietic, anticonvulsant and antidepressant drugs, while classified as barbiturates, benzadiazaepines, butyrophenones and phenothiazines according to the structure. The data handling was performed by a NEC9801Vm2 personal computer and data processor(DP-L320,Jasco) the data processing functions are three-dimensional chromatogram, contour chromatogram, peak deconvolution and so on. … More UV spectra of the drugs at the apex of the chromatographic peaks were stored in a spectrum library. Also in MULTI-HPLC system could be used an automated identification system based on the retention prediction concept, proposed by jinno(Toyohashi Univ.of Technology, School of Materials Science). The log Pe data file on sixty-five drugs were prepared. Rerention(T_r ), UV spectral, optimum wavelength and detection limit data of each drug were listed. The relation between sixty-five standard drug concentrations and peak area ratio was linear from 1 to 1000ng/ml. Peak deconvolution technique was applied to unresolved multi component peak analysis. Recoveries of sixty-five drugs from serum or urine were examine to compare following four exstraction procedures ; CH_3 CN deproteinization, ULTRA-FREE^Rfiltration, TOXI-TUBE^R extraction, Bond-ELUT^r elution method.possible application of the system were demonstrated using gastric contents, sera and urines in drug poisoning cases. In most cases at least more than six drugs were identified. Because the poisoned patients were often in a state of deep coma on arrival at Critical Care Medical Center, Nippon Medical School, no information of the toxic substances was obtained at the onset of the analysis. MULTI-HPLC system is considered useful for toxicological drug screening in the cases of "polydrug overdose" or "mulltiple drug ingestion" in which caseshave been unable to bve analyzed by the convetional HPLC analysis. Although the system in its present form will leave many problems to be solve in practice, the concept opens a new dimension of emergency toxicology. Less

本文介绍了一种新的用于有毒药物分离鉴定的应急药物筛选系统--“MULTI-HPLC”。使用的HPLC系统包括Model 880-PU泵和Multi-320多通道UV检测器（Jasco）。柱为Jasco FineSil C18 S（250mmx4.6mmI.D.）设定在50摄氏度。移动的流动相为10 mM高氯酸、10 mM高氯酸钠和乙腈的混合液，流速为1 ml/min。根据药理作用可分为抗精神病、抗焦虑、抗惊厥和抗抑郁药物，根据结构可分为巴比妥类、苯并二氮杂卓类、丁酰苯酮类和吩噻嗪类。数据处理采用NEC 9801 Vm 2微机和数据处理器（DP-L320，Jasco），具有三维色谱、等高线色谱、峰反卷积等功能。 ...更多信息将色谱峰顶点处药物的UV光谱存储在光谱库中。此外，在MULTI-HPLC系统中，可以使用由jinno（Toyohashi Univ.of Technology，School of Materials Science）提出的基于保留预测概念的自动识别系统。准备了65种药物的log Pe数据文件。列出了各药物的保留时间（Tr）、紫外光谱、最佳检测波长和检出限数据。在1 ~ 1000 ng/ml范围内，65种标准药物浓度与峰面积比呈良好的线性关系。将峰去卷积技术应用于多组分峰的分离分析。本文比较了乙腈脱蛋白法、超滤法、TOXI-TUBE法、Bond-ELUT法四种提取方法对65种药物的回收率，并以胃内容物、血清和尿液为例，说明了该系统的应用价值。在大多数情况下，至少确定了六种以上的药物。由于中毒患者在到达日本医科大学重症监护医疗中心时通常处于深度昏迷状态，因此在分析开始时没有获得有毒物质的信息。多效高效液相色谱系统可用于常规高效液相色谱分析方法无法分析的“多种药物过量”或“多种药物摄入”的毒理学药物筛选。尽管该系统目前的形式在实践中会留下许多问题需要解决，但这一概念为应急毒理学开辟了一个新的维度。少