Martínez María A, Ballesteros Salomé, Sánchez de la Torre Carolina, Almarza Elena
Chemistry Department, National Institute of Toxicology and Forensic Sciences, Ministry of Justice, C/ Luis Cabrera 9, 28002 Madrid, Spain.
J Anal Toxicol. 2005 May-Jun;29(4):262-8. doi: 10.1093/jat/29.4.262.
Trazodone is an antidepressant agent used in Spain since 1975. There are few documented reports of fatalities solely attributed to trazodone and none in which the main metabolite is analyzed. A fatal case of self-poisoning following oral ingestion is reported along with a description of the validated analytical methods involved, a discussion of poisoning characteristics, and a review of reports describing trazodone overdose cases with analytical results. The deceased was an 86-year-old man with cancer, who suffered depression. He went to see his doctor in a primary health care unit and told him he had just taken an unknown amount of tablets of Deprax to commit suicide. The doctor induced emesis as a first emergency measure. His death occurred before arriving to the hospital, and he left a suicide note nearby. Systematic toxicological analysis of postmortem blood used routinely in our laboratory revealed the presence of trazodone 4.9 mg/L and m-chlorophenyl-piperazine (m-CPP) 0.6 mg/L, its active and major metabolite. In addition, metamizol 19.6 mg/L and 4-methyl-amino-antipyrine (4-MAA) 40.7 mg/L, its active metabolite, were also found in blood. All drugs and metabolites involved in the case were detected using gas chromatography-nitrogen-phosphorus detection (GC-NPD) and confirmed using gas chromatography-mass spectrometry (GC-MS) mode total ion chromatogram. An additional high-performance liquid chromatography-diode array detection (HPLC-DAD) screening also obtained the same results. Quantitation of trazodone together with its metabolite in blood was carried out using GC-NPD, while quantitation of metamizol was performed using HPLC-DAD. Limits of detection for trazodone and m-CPP were 33 and 11 microg/L, respectively, absolute recoveries were more than 86% and 75%, respectively, intra-assay precisions less than 4%, interassay precisions less than 5%, and linearity up to 2.0 mg/L. Limit of detection for metamizol was 1117 microg/L, absolute recovery more than 84%, intra-assay precision less than 8%, interassay precision less than 12%, and linearity up to 48 mg/L. Based on the autopsy findings, patient history, toxicology results, and previously reported trazodone intoxications, the forensic pathologists ruled that the cause of death was due to an overdose of trazodone, and the manner of death was listed as suicide.
曲唑酮是一种自1975年起就在西班牙使用的抗抑郁药。仅有少数关于单纯由曲唑酮导致死亡的文献报道,且均未对主要代谢物进行分析。本文报告了一例口服曲唑酮自杀致死的案例,并描述了所采用的有效分析方法,讨论了中毒特征,还回顾了描述曲唑酮过量案例及分析结果的报告。死者是一名86岁患癌症的男性,患有抑郁症。他前往初级保健单位就医,告知医生自己刚刚服用了未知数量的德普雷克斯(Deprax)片剂企图自杀。医生首先采取催吐作为急救措施。他在抵达医院前死亡,附近留有一封遗书。我们实验室常规用于死后血液的系统毒理学分析显示,血液中存在曲唑酮4.9毫克/升以及其活性主要代谢物间氯苯基哌嗪(m-CPP)0.6毫克/升。此外,血液中还发现了安乃近19.6毫克/升及其活性代谢物4-甲基氨基安替比林(4-MAA)40.7毫克/升。该案例中涉及的所有药物和代谢物均采用气相色谱-氮磷检测(GC-NPD)进行检测,并通过气相色谱-质谱联用(GC-MS)模式的总离子色谱图进行确认。另外,高效液相色谱-二极管阵列检测(HPLC-DAD)筛查也得到了相同结果。使用GC-NPD对血液中的曲唑酮及其代谢物进行定量,使用HPLC-DAD对安乃近进行定量。曲唑酮和m-CPP 的检测限分别为33和11微克/升,绝对回收率分别超过86%和75%,批内精密度小于4%,批间精密度小于5%,线性范围高达2.0毫克/升。安乃近的检测限为11,17微克/升,绝对回收率超过84%,批内精密度小于8%,批间精密度小于12%,线性范围高达48毫克/升。基于尸检结果、患者病史、毒理学结果以及先前报道的曲唑酮中毒案例,法医病理学家判定死亡原因是曲唑酮过量,死亡方式列为自杀。