目的: 优化并建立一种快速检验血液和尿液中12个苯二氮䓬类药物的实时直接分析串联质谱(direct analysis of real time,DART-MS/MS)方法,使其能够用于法医毒物检验工作。方法: 使用DART离子源与API4000 Q Trap质谱仪联用;装载DART 12Dip-ItTM自动进样模块,模块移动速度为0.6 mm·s-1,进样量为5 μL,栅极电压为200 V;质谱部分在正离子模式下使用多反应监测(MRM)模式扫描监测。进一步优化DART-MS/MS条件后建立的方法经过方法学验证,并应用于实际案例检材。结果: 选用乙酸乙酯为萃取剂进行液液萃取,优化载气加热器温度;该方法选择性良好,无延迟效应;线性关系良好,血液和尿液中目标物检测限分别在0.5~10 ng·mL-1和0.2~2 ng·mL-1,定量限分别在1~50 ng·mL-1和 0.5~5 ng·mL-1;回收率在78.8%~119.0%,基质效应在-17.5%~18.5%;高、中浓度的日内、日间精密度与重复性不大于14.4%,定量限不大于18.1%。结论: 该方法快速简便,灵敏度良好,可应用于毒物快速检验研究与工作,提高检验效率。
Objective: To establish and optimize a rapid direct analysis of real time tandem mass spectrometry (DART-MS/MS) method for the rapid detection of 12 benzodiazepines in blood and urine that can be used in forensic toxicology work. Methods: A DART ion source was used in conjunction with an API4000 Q Trap mass spectrometer. A DART 12Dip-ItTM autosampling module with a module travel speed of 0.6 mm·s-1, a sample volume of 5 μL, and a gate voltage of 200 V were applied. The mass spectrometry section scans in positive ion mode using multiple reaction monitoring (MRM) mode. After further optimization, the DART-MS/MS method was validated and applied to real case samples. Results: Ethyl acetate was selected as the extractant for liquid-liquid extraction and the temperature of the carrier gas heater was optimized. The method has good selectivity and does not interfere with delayed effects. The linearity was good, and the limits of detection (LODs) for the targets in blood and urine were in the ranges of 0.5-10 ng·mL-1 and 0.2-2 ng·mL-1, respectively. And the limits of quantification (LOQs) were in the ranges of 1-50 ng·mL-1 and 0.5-5 ng·mL-1, respectively. The recoveries ranged from 78.8% to 119%, and the matrix effects ranged from -17.5% to 18.5%. The intra- and inter-day precisions were not greater than 14.4% for the high and intermediate concentrations, and not greater than 18.1% at the limits of quantification. This method enables fast and accurate examination of case samples. Conclusion: The method is fast and convenient, with good sensitivity, and can be applied to the research and work of rapid detection of toxicants to improve the efficiency of detection.
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