Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Jul 15;1242:124196. doi: 10.1016/j.jchromb.2024.124196. Epub 2024 Jun 10.
Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in therapeutic doses, and if they were taken in accidental, intentional, or suicidal overdose scenarios. Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). The method enables simultaneous identification and quantification in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation exhibited excellent linearity across the concentration range for all analytes. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 9 % and 10 %, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated very high sensitivity, with limits of detection (LOD) as low as 0.01 ng/ml and limits of quantification (LOQ) as low as 0.04 ng/ml. Extraction recovery exceeded 57.5 % for all analytes except atenolol, and matrix effects were <17 % for all analytes except pindolol. Processed sample stability evaluations revealed consistent results with acceptable deviations for all analytes. In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples.
抗心律失常药和抗高血压药在法医分析中经常遇到，可能会出现以下问题：这些药物是否以治疗剂量给药？如果是，它们是在意外、故意还是自杀过量的情况下服用的？因此，开发并验证了一种新的分析方法，用于定量分析 35 种具有毒理学相关性的药物，包括抗高血压药和抗心律失常药（阿马林、氨氯地平、胺碘酮、阿替洛尔、比索洛尔、卡维地洛、可乐定、去乙基胺碘酮、地尔硫卓、多奈哌齐、多沙唑嗪、决奈达隆、艾司洛尔、氟卡尼、盐酸左旋氨氯地平、利多卡因、美托洛尔、奈比洛尔、尼莫地平、哌唑嗪、普罗帕酮、普萘洛尔、索他洛尔、乌拉地尔和维拉帕米）以及其他常见的联合用药（西地那非、他达拉非、阿托伐他汀、氯吡格雷、达泊西汀、美金刚、己酮可可碱、利伐沙班和依伐布雷定）。该方法采用液相色谱-串联质谱法（LC-MS/MS），能够在血液样本中同时进行鉴定和定量分析。验证结果表明，所有分析物的浓度范围均具有良好的线性。精密度和准确度均在可接受范围内，偏差和相对标准偏差（RSD）值始终低于 9%和 10%。选择性和特异性评估证实不存在任何污染物或共提取药物的干扰。该方法具有很高的灵敏度，检测限（LOD）低至 0.01ng/ml，定量限（LOQ）低至 0.04ng/ml。除阿替洛尔外，所有分析物的提取回收率均超过 57.5%，除吡哚醇外，所有分析物的基质效应均<17%。处理后样品稳定性评估结果表明，所有分析物的结果均一致，偏差在可接受范围内。此外，该方法还专门针对法医分析进行了测试。通过对两个真实人体尸检血液样本的分析，证明了该方法的适用性。
