The determination of the novel insomnia medication lemborexant using a validated liquid chromatography-tandem mass spectrometry method, and its quantitation in clinical and forensic samples.

IF 2.8 4区医学 Q2 TOXICOLOGY

Forensic Toxicology Pub Date : 2025-07-16 DOI:10.1007/s11419-025-00733-4

Brian Waters, Masato Masuda, Aya Matsusue, Masayuki Kashiwagi, Hikaru Hori, Kazuya Ikematsu, Shin-Ichi Kubo

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引用次数: 0

Abstract

Purpose: This study aims to detail the identification, confirmation, and quantitation of lemborexant from clinical and postmortem specimens using a validated LC-MS/MS method. Additionally, it investigates the tissue distribution of lemborexant in several postmortem cases.

Methods: Lemborexant was isolated from the plasma of hospital patients or the postmortem specimens of forensic autopsy cases. Extraction from 0.1 mL or 0.1 g of sample was achieved by a modified QuEChERS protocol. The analysis was performed by liquid chromatography-tandem mass spectroscopy (LC-MS/MS). The quantitation method was validated in whole blood using internationally accepted parameters based on ANSI/ASB Standard 036. A total of 8 clinical samples and 13 forensic autopsy cases were analyzed by the validated method.

Results: In clinical cases, lemborexant concentrations in plasma ranged from 2.7 to 225 ng/mL. Lemborexant concentrations in the blood of forensic autopsy cases ranged from below the lower limit of quantitation (2 ng/mL) to 276 ng/mL. The highest postmortem concentrations were found in liver, adipose tissue, pancreas, and kidney. The method demonstrated high recovery rates and precision, with no significant matrix effects or interferences from other drugs.

Conclusions: The validated LC-MS/MS method proved effective for detecting and quantifying lemborexant in both clinical and forensic autopsy samples. The study highlights the importance of monitoring lemborexant and other dual orexin receptor antagonists (DORAs) in forensic investigations to understand their pharmacokinetics and potential toxicological effects.

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采用有效的液相色谱-串联质谱法测定新型失眠药物lemborexant，并在临床和法医样品中进行定量分析。

目的：本研究旨在使用经过验证的LC-MS/MS方法详细鉴定、确认和定量临床和死后标本中的lemborexant。此外，它还调查了几个死后病例中lemborexant的组织分布。方法：从医院患者血浆或法医尸检标本中分离Lemborexant。0.1 mL或0.1 g样品通过改进的QuEChERS方案进行提取。采用液相色谱-串联质谱（LC-MS/MS）分析。采用基于ANSI/ASB标准036的国际通用参数在全血中验证定量方法。采用验证的方法对8例临床标本和13例法医尸检病例进行了分析。结果：在临床病例中，血药浓度为2.7 ~ 225 ng/mL。法医尸检病例血液中Lemborexant的浓度从低于定量下限（2 ng/mL）到276 ng/mL不等。死后浓度最高的是肝脏、脂肪组织、胰腺和肾脏。该方法回收率高，精密度高，无明显基质效应，不受其他药物的干扰。结论：经验证的LC-MS/MS方法在临床和法医尸检样品中检测和定量香精是有效的。该研究强调了在法医调查中监测leleborexant和其他双食欲素受体拮抗剂（DORAs）的重要性，以了解它们的药代动力学和潜在的毒理学效应。

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).