Incorporation of suvorexant and lemborexant into hair and their distributions after a single intake.

IF 2.8 4区医学 Q2 TOXICOLOGY Forensic Toxicology Pub Date : 2024-08-09 DOI:10.1007/s11419-024-00700-5

Atsushi Nitta, Noriaki Shima, Hiroe Kamata, Misato Wada, Kengo Matsumoto, Hidenao Kakehashi, Shihoko Nakano-Fujii, Shuntaro Matsuta, Tooru Kamata, Munehiro Katagi, Takako Sato, Hiroshi Nishioka

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Abstract

Purpose: This study examined the applicability of hair analysis as an approach to identify suvorexant (SUV) and lemborexant (LEM) intake by analyzing black hair specimens collected from study participants after a single oral administration.

Methods: Hair specimens were collected form participants who took a single dose of 10 mg SUV or 5 mg LEM. Identification of the dual orexin receptor antagonists (DORAs) and their metabolites was performed by liquid chromatography-tandem mass spectrometry. Reference standards of S-M9 and L-M4, the metabolites of SUV and LEM, respectively, were synthesized in our laboratory. Sectional analysis of 1-mm segments of the single-hair strands was also performed to investigate the incorporation behavior of the drugs into hair.

Results: Unchanged SUV and LEM, and their metabolites S-M9 and L-M4 were detected even in the single-hair specimens. Results of the segmental hair analysis showed predominant incorporation of the drugs into hair through the hair bulb region rather than through the upper dermis zone of the hair root. The drug concentrations in the hair specimens, collected about 1 month after intake, were 0.033-0.037 pg/hair strand (0.17-0.19 pg/mg) for SUV and 0.054-0.28 pg/hair strand (0.28-1.5 pg/mg) for LEM. The calculated distribution ratios of the DORAs into hair to the oral doses were much lower than those of benzodiazepines and zolpidem reported in a previous study.

Conclusions: This is the first report of the detection of the DORAs in hair. The incorporation behavior of the DORAs into hair revealed herein are crucial for proper interpretation of hair test results.

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一次摄入后，毛发中的suvorexant和lemborexant及其分布情况。

目的：本研究通过分析研究对象单次口服给药后采集的黑色毛发标本，考察了毛发分析作为一种识别苏伐生坦（SUV）和廉博生坦（LEM）摄入量的方法的适用性。采用液相色谱-串联质谱法鉴定双重奥曲肽受体拮抗剂（DORAs）及其代谢物。我们实验室合成了 S-M9 和 L-M4 的标准物质，它们分别是 SUV 和 LEM 的代谢物。此外，还对单根头发的 1 毫米部分进行了截面分析，以研究药物在头发中的掺入行为：结果：即使在单根头发样本中也能检测到未发生变化的 SUV 和 LEM 及其代谢物 S-M9 和 L-M4。毛发分段分析结果显示，药物主要通过毛球区域而不是通过发根的真皮上层区域进入毛发。在摄入药物约 1 个月后采集的头发样本中，SUV 的药物浓度为 0.033-0.037 皮克/发丝（0.17-0.19 皮克/毫克），LEM 的药物浓度为 0.054-0.28 皮克/发丝（0.28-1.5 皮克/毫克）。计算得出的 DORAs 在头发中的分布比与口服剂量的分布比远远低于之前研究中报告的苯二氮卓和唑吡坦的分布比：这是首次报告在毛发中检测到 DORAs。本文揭示的 DORAs 在毛发中的掺入行为对于正确解释毛发检测结果至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Forensic Toxicology TOXICOLOGY-

CiteScore

5.80

自引率

9.10%

发文量

审稿时长

3 months

期刊介绍： The journal Forensic Toxicology provides an international forum for publication of studies on toxic substances, drugs of abuse, doping agents, chemical warfare agents, and their metabolisms and analyses, which are related to laws and ethics. It includes original articles, reviews, mini-reviews, short communications, and case reports. Although a major focus of the journal is on the development or improvement of analytical methods for the above-mentioned chemicals in human matrices, appropriate studies with animal experiments are also published. Forensic Toxicology is the official publication of the Japanese Association of Forensic Toxicology (JAFT) and is the continuation of the Japanese Journal of Forensic Toxicology (ISSN 0915-9606).