法医学杂志

法医学杂志 ›› 2021, Vol. 37 ›› Issue (1): 26-32.DOI: 10.12116/j.issn.1004-5619.2020.300402

• 论 著 • 上一篇    下一篇

超分子溶剂萃取-气相色谱-串联质谱法检测尿液中苯二氮䓬类药物

刘金磊1 ，顾捷2 ，陈丽琴2 ，阿民勿日他2   

  1. 1. 内蒙古医科大学研究生学院，内蒙古 呼和浩特 010059；2. 内蒙古医科大学法医教研室，内蒙古 呼和 浩特 010110
  • 收稿日期:2020-04-21 发布日期:2021-02-25 出版日期:2021-02-28
  • 通讯作者: 阿民勿日他，男，蒙古族，博士，讲师，主要从事法医毒物分析和法医毒理学研究；E-mail：31858044a@qq.com
  • 作者简介:刘金磊（1994－），男，硕士，主要从事法医毒物分析；E-mail：894998463@qq.com
  • 基金资助:
    国家自然科学基金资助项目（81860331）

Supramolecular Solvent Extraction-Gas Chromatography-Tandem Mass Spectrometry for Detection of Benzodiazepines in Urines

LIU Jin-lei1 , GU Jie2 , CHEN Li-qin2 , AMIN Wurita2   

  1. 1. Graduate School of Inner Mongolia Medical University, Hohhot 010059, China; 2. Department of Foren? sic Medicine, Inner Mongolia Medical University, Hohhot 010110, China
  • Received:2020-04-21 Online:2021-02-25 Published:2021-02-28

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摘要： 目的 建立一种尿液中9种苯二氮?类药物的超分子溶剂样品气相色谱-串联质谱（gas chroma? tography-tandem mass spectrometry，GC-MS/MS）分析方法。 方法 含9种苯二氮?类药物对照品的尿液样 品用四氢呋喃和1-己醇组成的超分子溶剂进行液液萃取，取溶剂层氮吹至干，残余物用甲醇复溶后进行 GC-MS/MS分析，数据采集方式为多反应监测模式，采用内标法定量。 结果 尿液中地西泮、咪达唑仑、氟 硝西泮和氯氮平质量浓度在1~100 ng/mL，劳拉西泮和阿普唑仑质量浓度在5~100 ng/mL，硝西泮和氯硝西 泮质量浓度在2~100 ng/mL，艾司唑仑在质量浓度0.2~100 ng/mL范围内具有良好的线性关系，相关系数为 0.999 1~0.999 9，定量下限为0.2~5 ng/mL，提取回收率为81.12%~99.52%，日内精密度［相对标准偏差（rela? tive standard deviation，RSD）］和准确度（偏倚）分别小于9.86%、9.51%；日间精密度（RSD）和准确度（偏倚） 分别小于8.74%、9.98%。室温和-20 ℃条件下，尿液中9种药物在15 d内具有良好的稳定性。8名志愿者单 摄口服阿普唑仑片后，在8~72 h内尿液中阿普唑仑的质量浓度为6.54~88.28 ng/mL。 结论 本研究建立的 尿液中9种苯二氮?类药物的超分子溶剂萃取-GC-MS/MS分析方法，简便、快速、准确、灵敏，可为临床治 疗及司法鉴定中苯二氮?类药物中毒监测提供技术支持。

关键词: 法医毒物化学, 气相色谱-串联质谱法, 苯二氮?类, 超分子溶剂, 尿液

Abstract: Objective To establish a method using supramolecular solvent and gas chromatography-tandem mass spectrometry （GC-MS/MS） to analyze 9 benzodiazepines in urines. Methods Urine samples containing 9 benzodiazepines reference substance were subjected to liquid-liquid extractions with supramolecular solvent, which consisted of tetrahydrofuran and 1-hexanol. The solvent layer was evaporated to dryness by stream of nitrogen. The residue was reconstituted with methanol, and GC-MS/MS analysis was performed on it. The way of data collection was multiple reaction monitoring （MRM） mode; internal standard method was employed for quantification. Results In urine samples, when the range of mass concentration was 1- 100 ng/mL for diazepam, midazolam, flunitrazepam and clozapine, 5- 100 ng/mL for lorazepam and alprazolam, 2-100 ng/mL for nitrazepam and clonazepam, and 0.2-100 ng/mL for estazolam, respectively, good linearities were obtained, correlation coefficients were 0.999 1-0.999 9, the lower limits of the quantifications ranged from 0.2 to 5 ng/mL, the extraction recovery rates were 81.12%- 99.52%. The intra-day precision［relative standard deviation（RSD）］and accuracy（bias）were lower than 9.86% and 9.51%, respectively; the inter-day precision（RSD）and accuracy（bias）were lower than 8.74% and 9.98% , respectively. Nine drugs in urine samples showed good stability at ambient temperature and -20 ℃ within 15 days. The mass concentrations of alprazolam in urine samples obtained from 8 volunteers who took alprazolam tablets orally within 8-72 h after ingestions ranged from 6.54 to 88.28 ng/mL.

Key words: forensic toxicology, gas chromatography-tandem mass spectrometer, benzodiazepines, supramolecular solvent, urin

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