Institute of Clinical Pharmacology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
J Chromatogr A. 2011 Jul 29;1218(30):4988-94. doi: 10.1016/j.chroma.2010.12.113. Epub 2011 Jan 5.
In this study it was possible to measure the distribution of metoprolol, tramadol, and midazolam in human directly in several compartments. In the legal medicine autopsy material is normally investigated to find out the cause of death. But the results of corresponding toxicology measurements often involve more information. With screening methods drugs were detected without connection to the cause of death. The deceased had either a continual therapeutic treatment, a treatment during an operation, or an unsuccessful urgent therapy. A liquid/liquid extraction and a LC/MS/MS method were developed for the determination of the drug concentrations. Different autopsy materials of about 120 cases were investigated. Most frequently the drugs metoprolol, tramadol, and midazolam could be proved and determined simultaneously. Metoprolol was found in seven cases, tramadol in seven cases and midazolam in thirteen cases. The dosage of the drugs was unknown. Therefore and because of the low number of cases statistic calculations were not meaningful and an individual case study was necessary. In all cases with oral metoprolol application the patients probably took a normal customary continuous dosage. The concentrations of tramadol in blood were in the toxic range in three cases. The distribution of tramadol in the compartments was independent of the dosage. The time between oral intake of metoprolol or tramadol and death was unknown. With the distribution pattern of metoprolol in the compartments it was possible to estimate the duration between drug intake and death. In most cases midazolam was given intravenously during an operation or an unsuccessful urgent therapy. Sometimes the time between dosage and death was documented. The duration between application of the drug and death played the crucial role for the distribution of midazolam in the compartments. Measurements of drug concentrations in human autopsy material deepen the knowledge of the respective drugs' pharmacokinetics.
在这项研究中，有可能直接在多个隔室中测量美托洛尔、曲马多和咪达唑仑在人体中的分布。在法医学尸检材料中，通常会进行调查以找出死因。但是，相应的毒理学测量结果通常涉及更多信息。使用筛选方法可以检测到与死因无关的药物。死者要么持续接受治疗，要么在手术期间接受治疗，要么接受不成功的紧急治疗。开发了一种液/液萃取和 LC/MS/MS 方法来测定药物浓度。对约 120 例不同的尸检材料进行了调查。最常被证明和同时确定的药物是美托洛尔、曲马多和咪达唑仑。在七种情况下发现了美托洛尔，七种情况下发现了曲马多，十三种情况下发现了咪达唑仑。药物剂量未知。因此，由于案例数量较少，统计计算没有意义，需要进行个案研究。在所有口服美托洛尔应用的病例中，患者可能服用了正常的常规连续剂量。三种情况下血液中曲马多的浓度处于毒性范围内。曲马多在隔室中的分布与剂量无关。口服美托洛尔或曲马多与死亡之间的时间未知。根据隔室中美托洛尔的分布模式，可以估计药物摄入和死亡之间的持续时间。在大多数情况下，咪达唑仑在手术或不成功的紧急治疗期间静脉给药。有时记录了剂量与死亡之间的时间。药物应用与死亡之间的时间间隔是咪达唑仑在隔室中分布的关键因素。人体尸检材料中药物浓度的测量加深了对各自药物药代动力学的了解。
