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Blood concentrations of designer benzodiazepines: Relation to impairment and findings in forensic cases.
Journal of Analytical Toxicology ( IF 2.3 ) Pub Date : 2020-05-05 , DOI: 10.1093/jat/bkaa043
Gunhild Heide 1 , Gudrun Høiseth 1, 2 , Gerrit Middelkoop 1 , Åse Marit Leere Øiestad 1
Affiliation  

The use of designer benzodiazepines appears to be increasing in many countries, but data concerning blood concentrations are scarce, making interpretation of concentrations difficult. The aim of this study was to report blood concentrations of clonazolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam and phenazepam and to investigate the relationship between blood concentrations and impairment. The concentration data are from blood samples collected from living cases (apprehended drivers and other drug offences) and medico-legal autopsies. The blood samples were analysed for the seven designer benzodiazepines mentioned above by ultra high performance liquid chromatography–tandem mass spectrometry. Positive cases from between 1 June 2016 and 30 September 2019 were included. Blood concentrations and the conclusion from a clinical test of impairment (when available) are reported. The presented seven benzodiazepines were detected in a total of 575 cases, where 554 of these cases concerned apprehended drivers or other criminal offenders. The number of findings and the median (range) concentrations were as follows: clonazolam, n = 22, 0.0041 mg/L (0.0017–0.053 mg/L); diclazepam, n = 334, 0.0096 mg/L (0.0016–0.25 mg/L); etizolam, n = 40, 0.054 mg/L (0.015–0.30 mg/L); flualprazolam, n = 10, 0.0080 mg/L (0.0033–0.056 mg/L); flubromazepam, n = 5, 0.037 mg/L (0.0070–0.70 mg/L); flubromazolam, n = 20, 0.0056 mg/L (0.0004–0.036 mg/L); and phenazepam, n = 138, 0.022 mg/L (0.0018–0.85 mg/L). A designer benzodiazepine was the only drug detected with relevance for impairment in 25 of the 554 living cases. The physician concluded with impairment in 19 of the 25 cases. Most of the concentrations in these cases were relatively similar to or higher than the median reported concentrations. The most frequent other drugs detected were amphetamine, tetrahydrocannabinol, clonazepam and methamphetamine. The presented blood concentrations can be helpful with the interpretation of cases involving one or more of these seven benzodiazepines. The results indicate that concentrations commonly observed in forensic cases are associated with impairment.

中文翻译:

设计师苯二氮卓类药物的血药浓度:与法医病例的损害和发现有关。

在许多国家/地区,设计师苯二氮卓类药物的使用似乎正在增加,但是有关血液浓度的数据很少,因此很难解释其浓度。这项研究的目的是报告可乐唑仑,地克西p,依替唑仑,氟吡唑仑,氟溴西epa,氟溴唑仑和非那西m的血药浓度,并研究血药浓度与损害之间的关系。浓度数据来自活体病例(被逮捕的驾驶员和其他毒品犯罪)和法医尸体解剖采集的血液样本。通过超高效液相色谱-串联质谱法对血样进行了上述七种设计师二苯并二氮杂卓的分析。包括2016年6月1日至2019年9月30日之间的阳性病例。报告了血药浓度和损伤临床试验的结论(如果有)。在总共575起案件中发现了所提出的7种苯并二氮杂where,其中554起涉及逮捕了驾驶员或其他犯罪分子。研究结果的数量和中位数(范围)浓度如下:氯氮唑仑,n  = 22,0.0041 mg / L(0.0017–0.053 mg / L);地拉西p,n  = 334,0.0096 mg / L(0.0016–0.25 mg / L); 依替唑仑,n  = 40,0.054 mg / L(0.015-0.30 mg / L); 氟哌唑仑,n  = 10,0.0080 mg / L(0.0033–0.056 mg / L);氟西epa,n  = 5,0.037 mg / L(0.0070–0.70 mg / L); 氟溴唑仑,n  = 20,0.0056 mg / L(0.0004-0.036 mg / L); 和非那西m,n = 138,0.022 mg / L(0.0018–0.85 mg / L)。在554例存活病例中的25例中,只有设计师设计的苯二氮卓类药物与损伤相关。在25例病例中,有19例医生得出结论。在这些情况下,大多数浓度相对高于或高于所报告的中值浓度。检出的最常见其他药物是苯丙胺,四氢大麻酚,氯硝西am和甲基苯丙胺。所提供的血药浓度有助于解释涉及这七个苯二氮卓中的一种或多种的病例。结果表明,在法医案件中通常观察到的浓度与损害有关。
更新日期:2020-05-05
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