Miami-Dade Medical Examiner Department, Toxicology Laboratory, 1851 NW 10th Ave., Miami, USA.
District 20 Medical Examiner Department, 3838 Domestic Ave., Naples, USA.
J Anal Toxicol. 2019 Sep 10;43(8):666-672. doi: 10.1093/jat/bkz061.
The (±)-threo-4-fluoromethylphenidate (4F-MPH) is a fluorinated analog of the prescription central nervous system stimulant medication, methylphenidate. This novel psychoactive substance was first detected in drug paraphernalia at the Miami-Dade County Medical Examiner Department Toxicology Laboratory in 2016 but was not detected in a biological specimen until 2018. Limited literature is available on 4F-MPH, with predominate literature being published out of Europe, and no known toxicities reported in the USA. Post-mortem specimens were screened using both gas chromatography mass spectrometry and liquid chromatography ion trap mass spectrometry (LC-Ion Trap-MSn). In addition, a validated method for the quantification of 4F-MPH was developed using liquid chromatography-tandem mass spectrometry (LC-MS-MS), with a linear range of 0.01-0.500 mg/L and acceptable validation criteria including precision, bias, carry-over, linearity and endogenous/exogenous interferences. In addition to the detection of 4F-MPH, 3-methoxy-PCP, amphetamine, methamphetamine, 6-monoacetylmorphine, morphine, codeine and tetrahydrocannabinol were also identified in the decedent. A single source of blood was collected (femoral vein) and quantified in all blood tubes used for collection, with concentrations varying from 0.012 to 0.05 mg/L. Additional specimens available for screening included gastric contents and urine. An additional peak having the same targeted ions and transitions as 4F-MPH was identified in both the LC-Ion Trap-MSn screening procedure and the LC-MS-MS quantitative procedure. This peak suggests the presence of a structural isomer, possibly (±)-erythro-4-fluoromethylphenidate, which cannot be confirmed due to there being no available certified reference material. This case report presents the first time that 4F-MPH was detected in a decedent, as well as the first time 4F-MPH has been listed in the official cause of death of a decedent in Florida.
（±）-threo-4-氟甲基苯丙胺（4F-MPH）是一种氟代的处方中枢神经系统兴奋剂哌甲酯的类似物。这种新型精神活性物质于 2016 年首次在迈阿密-戴德县法医部门毒理学实验室的药物用具中检测到，但直到 2018 年才在生物样本中检测到。关于 4F-MPH 的文献有限，主要文献来自欧洲，而在美国没有报告已知的毒性。使用气相色谱-质谱联用和液相色谱-离子阱质谱联用（LC-Ion Trap-MSn）对死后标本进行筛选。此外，还建立了一种用于定量检测 4F-MPH 的验证方法，使用液相色谱-串联质谱法（LC-MS-MS），线性范围为 0.01-0.500mg/L，具有可接受的验证标准，包括精密度、偏差、携带污染、线性和内源性/外源性干扰。除了检测到 4F-MPH 外，还在死者体内检测到 3-甲氧基-PCP、苯丙胺、甲基苯丙胺、6-单乙酰吗啡、吗啡、可待因和四氢大麻酚。从单一来源（股静脉）采集血液，并对用于采集的所有血液管进行定量，浓度从 0.012 到 0.05mg/L 不等。可用于筛选的其他样本包括胃内容物和尿液。在 LC-Ion Trap-MSn 筛选程序和 LC-MS-MS 定量程序中，都鉴定出一个具有与 4F-MPH 相同的靶向离子和跃迁的附加峰。该峰表明存在一种结构异构体，可能是（±）-赤式-4-氟甲基苯丙胺，但由于没有可用的认证参考物质，无法确认。本病例报告首次报道了 4F-MPH 在死者体内的检测，也是 4F-MPH 首次被列入佛罗里达州死者的官方死因。
