Klare Helge, Neudörfl Jörg M, Brandt Simon D, Mischler Elisabeth, Meier-Giebing Sigrid, Deluweit Kathrin, Westphal Folker, Laussmann Tim
Central Customs Authority, Centre of Education and Science, Merianstrasse 110, 50765, Cologne, Germany.
University of Cologne, Department of Chemistry, Organic Chemistry, Greinstrasse 6, 50939, Cologne, Germany.
Drug Test Anal. 2017 Mar;9(3):423-435. doi: 10.1002/dta.2161.
Six collected phenidates, i.e., 4-methylmethylphenidate, 3,4-dichloromethylphenidate, ethylphenidate, 3,4-dichloroethylphenidate, ethylnaphthidate, and N-benzyl-ethylphenidate were fully characterized by means of X-ray, nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), electrospray ionization-tandem mass spectrometry (ESI-MS/MS), attenuated total reflectance Fourier transform infrared (ATR-FTIR) and GC solid-state IR analysis. Crystallography revealed the exclusive presence of the threo-configuration. Steric crowding induced by N-benzyl substitution at the piperidine moiety prompted an adoption of an unexpected axial positioning of substituents on the piperidine moiety in the crystal state as opposed to the exclusive equatorial positioning encountered in N-unsubstituted phenidate analogues. Gas phase computations of the relative lowest energy conformers confirm that the axial positioning appears to be favoured over the equatorial positioning; in solution, however, equatorial positioning is predominant according to nuclear Overhauser effect experiments. All samples, mainly originating from China, had a good to very good degree of purity indicative of their professional chemical synthesis. Routine analysis of these drugs by GC-MS revealed thermal decomposition of phenidate analogues in the injection port and/or on column to 2-aryl-ethyl-acetates and 2,3,4,5-tetrahydropyridines. The decomposition pathway was suggested to proceed via a 6-membered transition state which was supported by density functional theory (DFT) computations. Fragmentation pathways of decomposition products as well as the corresponding electron ionization (EI) mass spectra are provided. The thermal instability might thus render smoking or 'vaping' of these drugs a less effective route of administration. The analytical fingerprints of six structurally diverse phenidate analogues provide a helpful reference to forensic chemists in charge of identifying new psychoactive substances. Copyright © 2017 John Wiley & Sons, Ltd.
六种收集到的哌醋甲酯类化合物，即4-甲基哌醋甲酯、3,4-二氯哌醋甲酯、乙基哌醋甲酯、3,4-二氯乙基哌醋甲酯、萘乙哌醋甲酯和N-苄基乙基哌醋甲酯，通过X射线、核磁共振（NMR）、气相色谱-质谱联用（GC-MS）、电喷雾电离串联质谱（ESI-MS/MS）、衰减全反射傅里叶变换红外光谱（ATR-FTIR）和GC固态红外分析进行了全面表征。晶体学研究表明，这些化合物仅存在苏式构型。哌啶部分的N-苄基取代所引起的空间拥挤，促使在晶体状态下哌啶部分的取代基采取了意想不到的轴向定位，这与未取代的哌醋甲酯类似物中仅有的赤道定位相反。相对最低能量构象体的气相计算证实，轴向定位似乎比赤道定位更受青睐；然而，根据核Overhauser效应实验，在溶液中赤道定位占主导。所有样品主要来自中国，纯度良好至非常高，表明它们是通过专业化学合成得到的。通过GC-MS对这些药物进行常规分析发现，哌醋甲酯类似物在进样口和/或柱上热分解为2-芳基乙酸乙酯和2,3,4,5-四氢吡啶。据推测，分解途径是通过一个六元过渡态进行的，这得到了密度泛函理论（DFT）计算的支持。文中提供了分解产物的碎裂途径以及相应的电子电离（EI）质谱。因此，热不稳定性可能使这些药物的吸烟或“ vaping”给药途径效果较差。六种结构不同的哌醋甲酯类似物的分析指纹图谱为负责鉴定新型精神活性物质的法医化学家提供了有用的参考。版权所有© 2017 John Wiley & Sons, Ltd.
