Quantification of fluvoxamine, desmethyl fluvoxamine and fluvoxamine acid by LC–MS/MS in body fluids and solid tissues obtained from a deceased using the standard addition method

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine Pub Date : 2025-10-01 Epub Date: 2025-08-30 DOI:10.1016/j.legalmed.2025.102684

Hideki Nozawa , Kayoko Minakata , Itaru Yamagishi , Kenta Yuyama , Masako Suzuki , Osamu Suzuki , Takuya Kitamoto , Minako Kondo , Koutaro Hasegawa

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引用次数: 0

Abstract

Reports on the quantification of fluvoxamine (FLV) in human tissues have been quite limited, although FLV has been used as an antidepressant since 1986. Fluvoxamine acid (FLA) was shown to be the major metabolite of FLV in human urine in 1983, but its quantification is also limited to only three works using human plasma. The existence of desmethyl fluvoxamine (FLD) in human specimens was recently reported in 2025; therefore, its quantification has not yet been performed. Therefore, the present work deals with the quantifications of FLV, FLD and FLA in the human samples of blood, cerebrospinal fluid, pericardial fluid, bile, urine, liver, kidney and cerebrum obtained from a human cadaver; for the quantification, the standard addition method was employed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The three top concentrations of FLV, FLD and FLA were observed in bile > liver > cerebrum, bile > liver > kidney and bile > kidney > urine, respectively. The three top relative ratios of FLD/FLA were observed in cerebrum > liver > bile, and the lowest ratio was observed in urine, and this may be one of the reasons why the previous work on FLV metabolites using urine in 1983 could not detect FLD. To our knowledge, this is the first report on the validated quantification of the new metabolite FLD by LC–MS/MS in the authentic human body fluids and solid tissues.

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采用LC-MS /MS法定量测定死者体液和固体组织中的氟伏沙明、去甲基氟伏沙明和氟伏沙明酸

尽管氟伏沙明自1986年以来一直被用作抗抑郁药，但关于人体组织中氟伏沙明（FLV）定量的报告相当有限。氟伏沙明酸（FLA）在1983年被证明是人尿中FLV的主要代谢物，但其定量也仅限于使用人血浆的三个工作。最近在2025年报告了人类标本中存在去甲基氟伏沙明（FLD）；因此，尚未对其进行量化。因此，本工作涉及从人体尸体中获得的血液、脑脊液、心包液、胆汁、尿液、肝脏、肾脏和大脑样本中FLV、FLD和FLA的定量分析；定量采用液相色谱-串联质谱法（LC-MS /MS）。FLV、FLD和FLA浓度最高的3个部位分别为胆肝脑、胆肝肾和胆肾尿。FLD/FLA的相对比值最高的三个部位出现在大脑、肝脏和胆汁中，最低的部位出现在尿液中，这可能是1983年用尿液检测FLV代谢物未能检测到FLD的原因之一。据我们所知，这是第一个通过LC-MS /MS对真实人体体液和固体组织中新的代谢物FLD进行有效定量的报告。

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

Legal Medicine Nursing-Issues, Ethics and Legal Aspects

CiteScore

2.80

自引率

6.70%

发文量

119

审稿时长

7.9 weeks

期刊介绍： Legal Medicine provides an international forum for the publication of original articles, reviews and correspondence on subjects that cover practical and theoretical areas of interest relating to the wide range of legal medicine. Subjects covered include forensic pathology, toxicology, odontology, anthropology, criminalistics, immunochemistry, hemogenetics and forensic aspects of biological science with emphasis on DNA analysis and molecular biology. Submissions dealing with medicolegal problems such as malpractice, insurance, child abuse or ethics in medical practice are also acceptable.