Quantification of direct‐acting oral anticoagulants: Application of a clinically validated liquid chromatography‐tandem mass spectrometry method to forensic cases,Drug Testing and Analysis

当前位置： X-MOL 学术 › Drug Test. Anal. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Quantification of direct‐acting oral anticoagulants: Application of a clinically validated liquid chromatography‐tandem mass spectrometry method to forensic cases
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2020-09-22 , DOI: 10.1002/dta.2930
Martin H J Wiesen ₁ , Cornelia Fietz ₁ , Martin Jübner ₂ , Stefanie Iwersen-Bergmann ₃ , Hilke Andresen-Streichert ₂ , Carsten Müller ₁ , Thomas Streichert _{1,

4}

Affiliation

In certain forensic cases, a quantification of direct‐acting oral anticoagulants (DOACs) can be necessary. We evaluate the applicability of a previously described liquid chromatography–tandem mass spectrometry (LC‐MS/MS) methodology for the determination of DOACs in plasma to postmortem specimen. Postmortem internal quality control (PIQC) samples were prepared in pooled blank postmortem heart blood, femoral blood, cerebrospinal fluid (CSF), and urine as well in plasma. To examine the application of the clinical method to forensic cases, the main validation parameters were reinvestigated using PIQC samples. Postmortem samples of 12 forensic cases with evidence of previous rivaroxaban intake and unknown bleeding disorders were analyzed. Interday variability remained within the acceptance criterion of ±15%. Matrix effects were comparable in blank plasma and postmortem matrix extracts. After 4 weeks of storage in the refrigerator, no relevant decrease of DOACs was evident. After 96 h of storage at room temperature, a slight decrease in edoxaban concentration was observed in CSF and urine, while plasma edoxaban decreased by about 50%. Median (range) rivaroxaban concentrations determined in specimen of forensic cases were as follows: heart blood (n = 6), 17.2 ng/ml (<LOQ, 56.6 ng/ml); femoral blood (n = 12), 27.6 ng/ml (<LOQ, 110.5 ng/ml); CSF (n = 7), 11.7 ng/ml (<LOQ, 17.5 ng/ml); urine (n = 6), 275.7 ng/ml (14.5–870.9 ng/ml). The median heart/femoral blood rivaroxaban ratio was 1.2 (n = 5). Exemplary, a forensic case with detection of edoxaban in femoral blood, CSF, and urine, is presented. DOACs can be detected in postmortem heart and femoral blood, CSF, and urine specimen by LC‐MS/MS. Based on limited forensic cases, no significant redistribution was evident for rivaroxaban, which was found at highest concentrations in urine.

中文翻译：

直接作用口服抗凝剂的量化：临床验证的液相色谱-串联质谱法在法医案件中的应用

在某些法医案例中，可能需要对直接作用口服抗凝剂 (DOAC) 进行量化。我们评估了先前描述的液相色谱-串联质谱 (LC-MS/MS) 方法在测定血浆中至死后标本中的 DOAC 的适用性。死后内部质量控制 (PIQC) 样品是在混合的空白死后心脏血、股血、脑脊液 (CSF) 和尿液以及血浆中制备的。为了检查临床方法在法医案例中的应用，使用 PIQC 样本重新研究了主要验证参数。分析了 12 例法医案件的尸检样本，这些案件具有先前服用利伐沙班的证据和未知的出血性疾病。日间变异保持在±15% 的可接受标准内。空白血浆和死后基质提取物中的基质效应相当。在冰箱中储存 4 周后，DOAC 没有明显减少。在室温下储存 96 小时后，在脑脊液和尿液中观察到依度沙班浓度略有下降，而血浆依度沙班下降了约 50%。法医案件样本中确定的利伐沙班浓度中位数（范围）如下：n = 6), 17.2 ng/ml (<LOQ, 56.6 ng/ml); 股血 ( n = 12)，27.6 ng/ml (<LOQ，110.5 ng/ml)；CSF ( n = 7)，11.7 ng/ml (<LOQ，17.5 ng/ml)；尿液 ( n = 6)，275.7 ng/ml (14.5–870.9 ng/ml)。中位心脏/股血利伐沙班比值为 1.2 ( n = 5)。举例说明了在股血、脑脊液和尿液中检测到依度沙班的法医案例。DOAC 可以通过 LC-MS/MS 在死后心脏和股骨血、脑脊液和尿液样本中检测到。根据有限的法医案例，利伐沙班在尿液中的浓度最高时没有明显的重新分布。

更新日期：2020-09-22

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11