Department of Legal Medicine, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.
Int J Legal Med. 2013 Nov;127(6):1101-7. doi: 10.1007/s00414-013-0843-6. Epub 2013 Mar 28.
Most of the daily work of forensic toxicologists deals with fatal cases resulting from overdoses of licit and illicit drugs. However, another reason for fatalities in patients suffering from epilepsy can be undetectable or subtherapeutic levels of antiepileptic drugs. Some studies have shown a correlation between "sudden unexpected death in epilepsy" (SUDEP) and the ineffective treatment of epilepsy. Low levels of antiepileptic drugs may be a risk factor for SUDEP. The death of a psychiatric patient also suffering from epilepsy inspired the investigation. Subsequent to the death of the patient, the doctor was accused of providing inadequate therapy for epilepsy. The patient was to be treated with valproic acid. We developed and validated a simple method of determining valproic acid levels by gas chromatography-mass spectrometry for serum, but a transfer of the method from serum to postmortem whole blood failed. The method had to be modified and revalidated for postmortem whole blood specimens. A stability study of valproic acid in postmortem blood was conducted, showing a decline of valproic acid levels by 85 % after storage at room temperature for 28 days. During the storage time, the blood samples showed changes in consistency. Depending on the stage of decomposition, it is necessary to perform a determination by standard addition with an equilibration time of 4 h before extraction to achieve reliable results. For a proper interpretation of quantitative results, it is necessary to keep the postmortem decline of valproic acid concentrations in mind.
法医毒物学家的日常工作大多涉及因滥用和非法药物过量导致的致命病例。然而，癫痫患者死亡的另一个原因可能是抗癫痫药物无法检测到或低于治疗剂量。一些研究表明，“癫痫猝死”（SUDEP）与癫痫治疗无效之间存在相关性。抗癫痫药物水平低可能是 SUDEP 的一个危险因素。一位同时患有癫痫的精神病患者的死亡激发了这项调查。在患者死亡后，医生被指控对癫痫提供了不充分的治疗。该患者本应接受丙戊酸治疗。我们开发并验证了一种通过气相色谱-质谱法测定血清中丙戊酸水平的简单方法，但该方法从血清转移到死后全血时失败了。该方法必须针对死后全血标本进行修改和重新验证。对死后血液中的丙戊酸稳定性进行了研究，结果表明，在室温下储存 28 天后，丙戊酸水平下降了 85%。在储存过程中，血液样本的稠度发生了变化。根据分解阶段的不同，有必要在提取前进行 4 小时的平衡时间进行标准添加测定，以获得可靠的结果。为了正确解释定量结果，必须注意死后丙戊酸浓度的下降。
