Indirect chiral separation of 8 novel amphetamine derivatives as potential new psychoactive compounds by GC-MS and HPLC

•Synthesis of 8 novel amphetamine derivatives•Indirect chiral separation with GC-MS and HPLC•Comparison of two different chiral derivatization agents•Use of MTPA and (R)-(−)-menthylchloroformate as agents

Amphetamine and its derivatives gained high popularity on the illegal drug market. In the last few years, a lot of new psychoactive compounds structurally related to amphetamine, such as 4-fluoroamphetamine and 4-fluoromethamphetamine swamped the drug market. They were designed to circumvent prohibition of amphetamine and N-methylamphetamine and are distributed via the Internet. Often, a halogen atom is introduced into the phenyl ring of amphetamine to turn the illegal amphetamine legal. Since amphetamines possess a chiral centre, two enantiomers are available, which might differ in activity. Since most of them are partially not commercially available to date, synthesis and characterisation of amphetamine derivatives might help authorities to identify these substances of abuse.The aim of this study was to investigate self-synthesized amphetamines concerning their identity and their enantiomeric status either by GC-MS or by HPLC. For GC-MS, derivatization with (R)-(+)-α-methoxy-α-trifluoromethylphenylacetic acid (MTPA) or (1R)-(−)-menthylchloroformate prior to analysis on a HP-5MS column was done. For chiral separation by HPLC a LiChrospher 100 RP-18e column and sulfated beta-cyclodextrin added to the mobile phase as chiral selector were used. Enantioseparation was accomplished successfully by both methods. Furthermore, simultaneous chiral separation of three positions isomers, namely 2-fluoroamphetamine, 3-fluoroamphetamine and 4-fluoroamphetamine, was shown successfully by HPLC.

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