The development of new sample preparation alternatives in analytical toxicology leading to quick, effective, automated and environmentally friendly procedures is growing in importance. One of these alternatives is the QuEChERS, originally developed for the analysis of pesticide residues, producing cleaner extracts than liquid-liquid extraction, and easier separation of aqueous and organic phases. However, there are few published studies on the miniaturization of this technique for forensic toxicology, especially in postmortem analysis. We developed and validated a modified micro-QuEChERS and LC–MS-MS assay to quantify 16 antidepressants, seven antipsychotics and three metabolites, and semi-quantify norfluoxetine and norsertraline in postmortem blood. The calibration curve was linear from 1–500 ng/mL, achieved a r>0.99, with all standards quantifying within ±15% of target except ±20% at the limit of quantification (LOQ) of 1 ng/mL for 26 substances. The F test was applied to evaluate if the variance between replicates remained constant for all calibrators. Six weighting factors were analyzed (1/x, 1/x², 1/x^0,5, 1/y, 1/y², 1/y^0,5), with the weighting factor with the lowest sum of residual regression errors (1/x²) selected. No endogenous or exogenous interferences were observed. Method imprecision and bias were less than 19.0% and 19.7%, respectively. Advantages of this method include a low sample volume of 100 µL, simple but effective sample preparation and a rapid 8.5 min run time. The validated analytical method was successfully applied to the analysis of 100 authentic postmortem samples.

中文翻译：

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改进的 Micro-QuEChERS 和 LC-MS-MS 对死后血样中 28 种精神药物定量方法的开发和验证

在分析毒理学中开发新的样品制备替代方案，从而实现快速、有效、自动化和环保的程序变得越来越重要。其中一种替代方案是 QuEChERS，最初开发用于分析农药残留，产生比液-液萃取更清洁的萃取物，并且更容易分离水相和有机相。然而，关于法医毒理学，尤其是尸检分析的这种技术小型化的已发表研究很少。我们开发并验证了一种改进的微型 QuEChERS 和 LC-MS-MS 测定法，以量化 16 种抗抑郁药、7 种抗精神病药和 3 种代谢物，并对死后血液中的去甲氟西汀和去甲舍曲林进行半定量。校准曲线在 1–500 ng/mL 范围内呈线性，达到 r>0.99，26 种物质的定量限 (LOQ) 为 1 ng/mL，除 ±20% 外，所有标准品的定量均在目标值的 ±15% 以内。F 检验用于评估所有校准品的重复之间的差异是否保持不变。分析了六个加权因子（1/x、1/x² , 1/x ^0,5 , 1/y, 1/y ² , 1/y ^0,5 )，选择具有最低残差回归误差总和 (1/x ² )的加权因子。未观察到内源性或外源性干扰。方法不精密度和偏差分别小于 19.0% 和 19.7%。这种方法的优点包括 100 µL 的低样品体积、简单但有效的样品制备和 8.5 分钟的快速运行时间。经验证的分析方法已成功应用于 100 个真实死后样本的分析。