Recently, the new psychoactive substance (NPS) ketamine analogue 2-fluoro-deschloroketamine (2FDCK) was observed in driving-under-the-influence-of-drugs whole blood samples and in a forensic hair investigation case in Denmark. The molecular structure variations among the NPS subgroups may alter the metabolic fate and drug potency, thereby posing a threat for drug users. This study reports quantification of 2FDCK in whole blood samples and forensic hair and compares the following toxicokinetic parameters: unbound fraction (fu) and in vitro-in vivo-extrapolation (IVIVE) of hepatic clearance for ketamine, norketamine, 2FDCK, methoxetamine and deschloroketamine. The fu was investigated with ultrafiltration, while clearance studies were conducted at 1 μM with pooled human liver microsomes. Samples were analysed by liquid chromatography and mass spectrometry. For the first time, 2FDCK was determined in a concentration range between 0.005 and 0.48 mg/kg in blood samples. Segmental hair analysis demonstrated 2FDCK at concentrations from 0.007 to 0.034 ng/mg throughout the three investigated segments. Toxicokinetic comparison of the five compounds gave a fu between 0.54 and 0.84, with ketamine being the most bound and deschloroketamine being the least bound, in accordance with the logP of the compounds. Conversely, a negative correlation was observed between the molecular weight of the halogen in the ortho-position and IVIVE hepatic clearance. The IVIVE of hepatic clearance, CLparallel-tube, gave values from 18.1 to 5.44 mL/min/kg for ketamine and methoxetamine, respectively. The deschloroketamine IVIVE was disregarded due to low drug elimination under the experimental conditions used. This study provides a basis for toxicokinetic understanding of ketamine analogues.

中文翻译：

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氯胺酮类似物：法医血液和头发样本中2-氟脱氯氯胺酮的体外，体内毒性动力学比较和定量。

最近，在丹麦影响力十足的全血样本驾驶和法医头发调查中，观察到了新的精神活性物质（NPS）氯胺酮类似物2-氟-去氯氯胺酮（2FDCK）。NPS亚组之间的分子结构变化可能会改变代谢命运和药物效力，从而对吸毒者构成威胁。这项研究报告了全血样品和法医头发中2FDCK的定量，并比较了以下毒代动力学参数：氯胺酮，去甲氯胺酮，2FDCK，甲氧西丁胺和去氯代氯胺酮的肝清除率的未结合分数（fu）和体外体内体外外推（IVIVE）。使用超滤技术对fu进行了研究，同时对合并的人肝微粒体以1μM进行了清除研究。通过液相色谱和质谱分析样品。首次在血样中测定2FDCK的浓度范围为0.005至0.48 mg / kg。分段毛发分析表明，在整个三个研究片段中，2FDCK的浓度为0.007至0.034 ng / mg。根据化合物的logP，对这五种化合物的毒物动力学比较得出fu在0.54至0.84之间，氯胺酮结合最多，而去氯氯胺酮结合最少。相反，在邻位卤素的分子量与IVIVE肝清除率之间观察到负相关。氯胺酮和甲氧西敏的肝清除率IVIVE CL CL管分别为18.1 mL / min / kg / kg / min / kg / kg至5.44 mL / min / kg。由于在所使用的实验条件下药物去除率低，因此不考虑去氯氯胺酮IVIVE。该研究为氯胺酮类似物的毒代动力学理解提供了基础。