Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Hermann Staudinger Graduate School, University of Freiburg, Freiburg, Germany.
Drug Test Anal. 2019 Jul;11(7):1009-1017. doi: 10.1002/dta.2577. Epub 2019 Mar 20.
Pharmaceutical research not only provides the basis for the development of new medicinal products but also for the synthesis of new drugs of abuse. 3-Fluorophenmetrazine (3-FPM), a fluorinated derivative of the anorectic phenmetrazine, was first patented in 2011 and appeared on the drug market in 2014. Though invented for potential medical purposes, pharmacokinetic data on this compound, crucial for interpreting forensic as well as clinical cases, are not available. Therefore, a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the detection of 3-FPM in serum, urine, and oral fluid was developed, validated for urine and serum, and used to quantify 3-FPM in samples obtained during a controlled self-experiment. The method proved to be linear, selective and sufficiently sensitive. The limits of detection (LODs) were 0.1 ng/mL, 0.2 ng/mL, and 0.05 ng/mL in serum, urine, and oral fluid. Inter-day precision and intra-day precision (RSD) in serum samples were below 6.3% and below 8.5%, respectively. The highest serum concentration (c ) of 210 ng/mL was reached 2.5 hours (t ) after ingestion. The elimination half-life and the volume of distribution were calculated to be approx. 8.8 hours and 400 L (5.3 L/kg). 3-FPM could be detected in serum and urine up to 82 hours and 116 hours, respectively. It was still detected in the last oral fluid sample taken 55 hours after ingestion. 3-FPM was mainly excreted unchanged. Main metabolic reactions were aryl-hydroxylation and N-hydroxylation. Interestingly, the product of oxidative ring opening (2-amino-1-(3-fluorophenyl)propan-1-ol) showed the largest window of detection in the self-experiment.
药物研究不仅为新药物的合成提供了基础，也为新的滥用药物的合成提供了基础。3-氟苯丙胺（3-FPM）是一种厌食苯丙胺的氟化衍生物，于 2011 年首次获得专利，并于 2014 年出现在毒品市场上。虽然它是为潜在的医疗用途而发明的，但这种化合物的药代动力学数据对于解释法医和临床案例至关重要，但目前尚不可用。因此，开发了一种用于检测血清、尿液和唾液中 3-FPM 的液相色谱-电喷雾电离串联质谱（LC-ESI-MS/MS）方法，并对尿液和血清进行了验证，并用于对受控自我实验中获得的样品进行定量分析。该方法被证明是线性的、选择性的和足够敏感的。血清、尿液和唾液中的检测限（LOD）分别为 0.1ng/mL、0.2ng/mL 和 0.05ng/mL。血清样本的日内精密度和日间精密度（RSD）分别低于 6.3%和 8.5%。摄入后 2.5 小时达到最高血清浓度（c）210ng/mL。半衰期和分布体积计算约为 8.8 小时和 400L（5.3L/kg）。3-FPM 可在血清和尿液中分别检测到 82 小时和 116 小时。摄入后 55 小时，最后一次唾液样本仍能检测到 3-FPM。3-FPM 主要以原形排泄。主要代谢反应为芳基羟化和 N-羟化。有趣的是，氧化开环的产物（2-氨基-1-（3-氟苯基）-1-丙醇）在自我实验中表现出最大的检测窗口。
