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死后毒理学中生物分析程序的要求。

Requirements for bioanalytical procedures in postmortem toxicology.

作者信息

Drummer Olaf H

机构信息

Victorian Institute of Forensic Medicine, Department of Forensic Medicine, Monash University, Southbank, VIC 3006, Australia.

出版信息

Anal Bioanal Chem. 2007 Aug;388(7):1495-503. doi: 10.1007/s00216-007-1238-7. Epub 2007 Mar 23.

DOI:10.1007/s00216-007-1238-7
PMID:17377776
Abstract

The application of analytical techniques in postmortem toxicology is often more difficult than in other forms of forensic toxicology owing to the variable and often degraded nature of the specimens and the diverse range of specimens available for analysis. Consequently, analysts must ensure that all methods are fully validated for the particular postmortem specimen(s) used. Collection of specimens must be standardized to minimize site-to-site variability and should if available include a peripheral blood sample and at least one other specimen. Urine and vitreous humor are good specimens to complement blood. In some circumstances solid tissues such as liver are recommended as well as gastric contents. Substance-screening techniques are the most important element since they will determine the range of substances that were targeted in the investigation and provide initial indication of the possible role of substances in the death. While immunoassay techniques are still commonly used for the most common drugs-of-abuse, chromatographic screening methods are required for general unknown testing. These are still predominately gas chromatography (GC) based using nitrogen/phosphorous detection and/or mass spectrometry (MS) detection, although some laboratories are now using time-of-flight MS or liquid chromatography (LC)-MS(MS) to cover a sometimes more limited range of substances. It is recommended that laboratories include a second chromatographic method to provide coverage of acidic and other substances not readily covered by a GC-based screen when extracts do not include all physiochemical types. This may include a gradient high-performance liquid chromatography (HPLC) photodiode array method, or better LC-MS(MS). Substance-specific techniques (e.g., benzodiazepines, opiates) providing a second form of identification (confirmation) are now divided between GC-MS(MS) and LC-MS(MS) procedures. LC-MS(MS) has taken over from many methods for the more polar compounds previously used in HPLC or in GC methods requiring derivatization. Analysts using LC-MS will need to obtain clean extracts to avoid poor and variable sensitivity caused by background suppression of the signal. Isolation techniques in postmortem toxicology tend to favor liquid extraction; however solid-phase extraction and solid-phase microextraction methods are available for many analytes.

摘要

由于死后毒理学标本性质多变且常已降解,以及可用于分析的标本种类繁多,分析技术在死后毒理学中的应用往往比在其他形式的法医毒理学中更为困难。因此,分析人员必须确保所有方法针对所使用的特定死后标本进行了充分验证。标本的采集必须标准化,以尽量减少不同地点间的差异,如有可能,应包括一份外周血样本和至少一份其他标本。尿液和玻璃体液是补充血液的良好标本。在某些情况下,建议采集肝脏等固体组织以及胃内容物。物质筛查技术是最重要的环节,因为它们将确定调查中所针对的物质范围,并初步表明物质在死亡中可能所起的作用。虽然免疫分析技术仍常用于最常见的滥用药物检测,但一般未知物检测需要色谱筛查方法。这些方法仍然主要基于气相色谱(GC),使用氮/磷检测和/或质谱(MS)检测,不过现在一些实验室正在使用飞行时间质谱或液相色谱(LC)-MS(MS)来检测有时范围更有限的物质。建议实验室采用第二种色谱方法,以便在提取物未涵盖所有物理化学类型时,能够检测酸性物质和其他不易被基于GC的筛查所涵盖的物质。这可能包括梯度高效液相色谱(HPLC)光电二极管阵列法,或者更好的LC-MS(MS)。提供第二种鉴定(确证)形式的物质特异性技术(例如苯二氮䓬类、阿片类)现在分为GC-MS(MS)和LC-MS(MS)程序。LC-MS(MS)已取代了许多以前用于HPLC或需要衍生化的GC方法中检测极性较大化合物的方法。使用LC-MS的分析人员需要获得纯净的提取物,以避免信号背景抑制导致灵敏度不佳和变化。死后毒理学中的分离技术倾向于采用液液萃取;然而,固相萃取和固相微萃取方法也可用于许多分析物。

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