van der Meer Mikayla Zoë, Rasmussen Brian Schou, Nedahl Michael, Nielsen Marie Katrine Klose
Department of Forensic Medicine, Section of Forensic Chemistry, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Anal Toxicol. 2025 Apr 12;49(4):209-215. doi: 10.1093/jat/bkaf017.
Concentrations of amitriptyline and nortriptyline in postmortem blood samples may not accurately reflect the concentrations at the time of death due to postmortem redistribution or degradation. The brain is suggested as an alternative matrix since it is less subjected to postmortem redistribution and more protected against trauma and putrefaction, but reference concentrations in brain tissue are scarce. In this study, we aimed to provide concentrations in brain tissue and brain-blood ratios in 53 postmortem cases, where amitriptyline and/or nortriptyline were detected. To establish reference levels, each case was assigned to one of three classes according to the cause of death: (i) lethal intoxication by the sum of amitriptyline and nortriptyline or nortriptyline alone, (ii) lethal intoxication by the drugs in combination with other drugs, and (iii) the cause of death was not influenced by amitriptyline and/or nortriptyline. A positive correlation between blood and brain concentrations was found with a Spearman coefficient of 0.98. In 42 cases, where both drugs were detected, the 10-90 percentiles in brain tissue ranged from 0.17-9.1 mg/kg (median: 0.78 mg/kg) for amitriptyline and 0.22-5.0 mg/kg (median: 1.43 mg/kg) for nortriptyline across all classes. In 11 cases where only nortriptyline was detected, the percentiles ranged from 0.32-7.2 mg/kg (median: 0.28 mg/kg) in brain tissue. A median brain-blood ratio of 3.4 was found for amitriptyline, 8.5 for nortriptyline as a metabolite of amitriptyline and 9.7 for nortriptyline as an individual ingested drug. No significant difference was found between the different classes. The obtained brain concentrations and brain-blood ratio can contribute to the alternative or complementary use of brain tissue for future toxicological investigations.
由于死后再分布或降解，死后血液样本中阿米替林和去甲替林的浓度可能无法准确反映死亡时的浓度。有人建议将大脑作为替代基质，因为它较少受到死后再分布的影响，并且更能抵御创伤和腐败，但脑组织中的参考浓度却很稀少。在本研究中，我们旨在提供53例死后案例中脑组织中的浓度以及脑血比，这些案例中检测到了阿米替林和/或去甲替林。为了确定参考水平，根据死亡原因将每个案例分为三类之一：(i) 阿米替林和去甲替林之和或仅去甲替林导致的致死性中毒，(ii) 这些药物与其他药物联合导致的致死性中毒，以及(iii) 死亡原因不受阿米替林和/或去甲替林影响。发现血液和大脑浓度之间存在正相关，斯皮尔曼系数为0.98。在42例同时检测到两种药物的案例中，所有类别中脑组织中阿米替林的10 - 90百分位数范围为0.17 - 9.1毫克/千克（中位数：0.78毫克/千克），去甲替林为0.22 - 5.0毫克/千克（中位数：1.43毫克/千克）。在11例仅检测到去甲替林的案例中，脑组织中的百分位数范围为0.32 - 7.2毫克/千克（中位数：0.28毫克/千克）。发现阿米替林的脑血比中位数为3.4，去甲替林作为阿米替林代谢产物的脑血比为8.5，去甲替林作为单独摄入药物的脑血比为9.7。不同类别之间未发现显著差异。所获得的脑浓度和脑血比可为未来毒理学研究中脑组织的替代或补充使用提供帮助。
