Laboratory of Clinical Chemistry, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Laboratory of Environmental Hygiene and Forensic Toxicology, Department of Prevention, Azienda ULSS 3 Serenissima, Mestre, Veneto, Italy.
J Anal Toxicol. 2019 Jun 1;43(5):e1-e7. doi: 10.1093/jat/bkz001.
4-Fluoromethylphenidate (4F-MPH) is an halogenated derivative of methylphenidate (MPH), a re-uptake inhibitor for dopamine and norepinephrine used for the treatment of attention deficit hyperactivity disorders. In the last few years, several compounds structurally related to MPH have been marked as new psychoactive substances (NPS) with stimulating and euphoric effects similar to the parent drug, but with more dopaminergic activity. This report represents the first case of an analytically confirmed non-fatal intoxication by 4F-MPH. A 26-year-old female was admitted to the emergency department with neuropsychiatric and cardiologic symptoms that lasted for a week, during which she sniffed a powder named 4F-MPH acquired as entactogen on the Internet. The patient required sedation with intravenous diazepam and was discharged two days later with a prescription of promazine and quetiapine. The seized product was analytically characterized by gas chromatography-mass spectrometry, liquid chromatography high-resolution mass spectrometry and nuclear magnetic resonance. These analyses confirmed the composition of the product as a 4F-MPH diastereomeric (±)-threo and (±)-erythro mixture, with a large preponderance of the active (±)-threo isomer. A minimal validation, intended for rare analytes, was performed for the quantification of 4F-MPH in the biological samples by liquid chromatography-tandem mass spectrometry. Accuracy (bias) and precision were within ±15% for both blood and urine. The blood and urine concentration of (±)-threo 4F-MPH were 32 ng/mL and 827 ng/mL, respectively. Analyses for classic drugs (opiates, methadone, cocaine, cannabis metabolites, amphetamines, ecstasy and LSD), ethanol, qualitative full screen by gas chromatography-mass spectrometry and targeted analysis for 50 NPS by liquid chromatography-tandem mass spectrometry tested negative; comorbidities were excluded, too. Based on these data, it can be assumed that the clinical manifestations were due to 4F-MPH only.
4-氟甲基苯丙胺（4F-MPH）是哌醋甲酯（MPH）的卤代衍生物，MPH 是一种用于治疗注意力缺陷多动障碍的多巴胺和去甲肾上腺素再摄取抑制剂。在过去的几年中，几种结构上与 MPH 相关的化合物已被标记为具有刺激和欣快作用的新型精神活性物质（NPS），与母体药物相似，但具有更强的多巴胺能活性。本报告代表了首例经分析确认的非致命性 4F-MPH 中毒病例。一名 26 岁女性因神经精神和心脏症状被收入急诊病房，这些症状持续了一周，在此期间，她嗅了一种在互联网上购买的名为 4F-MPH 的粉末作为快感增强剂。患者需要静脉注射地西泮镇静，并在两天后出院，同时开了奋乃静和喹硫平的处方。缴获的产品通过气相色谱-质谱联用、液相色谱高分辨质谱和核磁共振进行了分析。这些分析证实该产品的成分是 4F-MPH 非对映异构体（±）-苏式和（±）-赤式混合物，其中活性（±）-苏式异构体占很大优势。对液相色谱-串联质谱法生物样本中 4F-MPH 的定量进行了最小验证，旨在对稀有分析物进行验证。血液和尿液的准确度（偏差）和精密度均在±15%以内。（±）-苏式 4F-MPH 的血液和尿液浓度分别为 32ng/ml 和 827ng/ml。经典药物（阿片类药物、美沙酮、可卡因、大麻代谢物、苯丙胺类、摇头丸和 LSD）、乙醇、气相色谱-质谱联用全谱定性分析和液相色谱-串联质谱靶向分析 50 种 NPS 的检测结果均为阴性；也排除了合并症。基于这些数据，可以假设临床表现仅与 4F-MPH 有关。
