Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V's vej 11, DK-2100, Denmark.
Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V's vej 11, DK-2100, Denmark.
Forensic Sci Int. 2020 Dec;317:110523. doi: 10.1016/j.forsciint.2020.110523. Epub 2020 Sep 23.
Segmental hair analysis provides information regarding previous long-term drug exposure, which is useful in the evaluation of cause of death for individuals with mental disorders. The aim was to analyze postmortem concentrations of the antipsychotic drug aripiprazole and its active metabolite dehydroaripiprazole in hair segments from individuals with known aripiprazole intake. Hair samples were collected during autopsy. Each sample was segmented into one to six 1cm segments, depending on the length of the hair shaft. Pulverized hair was extracted and analyzed using a previously published ultra-high-performance liquid chromatography-tandem mass spectrometric method. The 10th-90th percentile of aripiprazole concentrations in all hair segments (n=78) from 17 individuals were 0.024ng/mg-11ng/mg with a median of 2.3ng/mg, and the 10th-90th percentile concentrations of dehydroaripiprazole were 0.020ng/mg-11ng/mg, with a median of 2.6ng/mg, in all hair segments (n=71). The metabolite-to-parent drug ratios ranged from 0.21 to 1.5, with a median of 0.72. The administered doses were calculated for each individual based on aripiprazole prescription data and pharmacy pickups, giving dose estimates of 1mg-32mg daily. A positive significant correlation was observed between concentrations in hair and blood, whereas no trends were observed between the concentrations in hair and the estimated doses. Besides aripiprazole, other antipsychotic drugs were found in several hair segments, indicating a high degree of polypharmacy among all subjects. The present study establishes concentrations of aripiprazole and dehydroaripiprazole in hair segments from 17 deceased individuals with long-term aripiprazole use. In addition, hair analysis demonstrates the possibility of evaluating polypharmacy.
分段毛发分析提供了有关先前长期药物暴露的信息,这对于评估有精神障碍的个体的死因非常有用。目的是分析已知使用过阿立哌唑的个体毛发中抗精神病药物阿立哌唑及其活性代谢物脱氢阿立哌唑的死后浓度。在尸检期间采集了毛发样本。每个样本根据毛发轴的长度分为一到六个 1 厘米的段。将粉碎的毛发提取并使用先前发表的超高效液相色谱-串联质谱法进行分析。17 名个体的所有毛发段(n=78)中阿立哌唑浓度的第 10-90 百分位数为 0.024ng/mg-11ng/mg,中位数为 2.3ng/mg,而脱氢阿立哌唑浓度的第 10-90 百分位数为 0.020ng/mg-11ng/mg,中位数为 2.6ng/mg,所有毛发段(n=71)。代谢物与母体药物的比值范围为 0.21 至 1.5,中位数为 0.72。根据阿立哌唑处方数据和药房取药,为每个个体计算了给药剂量,估计每天 1mg-32mg。观察到毛发和血液中的浓度之间存在正显著相关性,而毛发中的浓度与估计剂量之间没有观察到趋势。除了阿立哌唑,在几个毛发段中还发现了其他抗精神病药物,表明所有受试者都存在高度的多药治疗。本研究建立了 17 名长期使用阿立哌唑的已故个体的毛发段中阿立哌唑和脱氢阿立哌唑的浓度。此外,毛发分析表明评估多药治疗的可能性。