Rab Edmund, Martin Stephanie, Freemont Anthony, Maslin Samantha, Marr Roger, Kanu Mohammad-Sadik
Specialised Clinical Chemistry, Sheffield Teaching Hospitals NHS Foundation Trust, Herries Road, Sheffield S5 7AU, United Kingdom.
University of Manchester and Manchester Academic Health Science Centre, Citylabs 1.0, Nelson Street, Manchester M13 9NQ, United Kingdom.
J Anal Toxicol. 2023 Apr 14;47(4):317-323. doi: 10.1093/jat/bkad011.
Screening of postmortem blood and urine samples is used to identify compounds that may have contributed to an individual's death. Toxicologically significant compounds detected by the screen are then quantitated in blood to determine their likely effect upon death. In most laboratories, this is a two-step process. This study compares an established two-step screening and quantitative processes, utilizing a gas chromatography-mass spectrometry (GC-MS) screen followed by quantitation by GC-MS or high-performance liquid chromatography with diode array detection (HPLC-DAD), with a novel method utilizing liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The LC-HRMS assay is able to screen postmortem blood and urine samples and simultaneously measure the concentration of toxicologically significant compounds in postmortem blood. Screening results of 200 postmortem blood samples and 103 postmortem urine samples by LC-HRMS and GC-MS showed that LC-HRMS detected key compounds in 125% more instances and there was a 60% increase in the number of compounds detected. Quantitative values generated using the LC-HRMS assay were within ±10% of values obtained using the established methods by GC-MS or HPLC-DAD. A retrospective analysis of turnaround times pre- and post-adoption of LC-HRMS showed a decrease for all of the compounds in the analysis, including a 43% reduction for free morphine and codeine, a 50% reduction for amphetamine and a 37% reduction for cocaine. Combining screening and quantitation reduced staffing requirements by 2 days for opiate quantitation and 1 day for most other analytes. The adoption of LC-HRMS also significantly reduced sample volume requirements. These results demonstrate that the adoption of LC-HRMS for simultaneous screening and quantitation delivered significant benefits in comparison to the two-step procedure.
对死后血液和尿液样本进行筛查，以识别可能导致个体死亡的化合物。然后对筛查中检测到的具有毒理学意义的化合物进行血液定量分析，以确定它们对死亡可能产生的影响。在大多数实验室中，这是一个两步过程。本研究将一种既定的两步筛查和定量方法（利用气相色谱 - 质谱联用仪（GC-MS）进行筛查，随后通过GC-MS或带二极管阵列检测的高效液相色谱法（HPLC-DAD）进行定量）与一种利用液相色谱 - 高分辨率质谱联用仪（LC-HRMS）的新方法进行了比较。LC-HRMS检测方法能够对死后血液和尿液样本进行筛查，并同时测量死后血液中具有毒理学意义的化合物的浓度。通过LC-HRMS和GC-MS对200份死后血液样本和103份死后尿液样本进行筛查的结果表明，LC-HRMS检测到关键化合物的情况多出125%，检测到的化合物数量增加了60%。使用LC-HRMS检测方法生成的定量值与使用GC-MS或HPLC-DAD既定方法获得的值相差在±10%以内。对采用LC-HRMS前后周转时间的回顾性分析表明，分析中的所有化合物的周转时间都有所减少，包括游离吗啡和可待因减少了43%，苯丙胺减少了50%，可卡因减少了3%。将筛查和定量相结合，阿片类药物定量所需人员减少了2天，大多数其他分析物所需人员减少了1天。采用LC-HRMS还显著降低了样本量要求。这些结果表明，与两步法相比，采用LC-HRMS进行同步筛查和定量带来了显著的益处。
