Various
cathinone-derived
designer drugs (CATs) have recently appeared on the
drug market. This study examined the mechanism for the generation of dehydrated
ions for CATs during electrospray ionization collision-induced dissociation (ESI-CID). The generation mechanism of dehydrated
ions is dependent on the
amine classification in the
cathinone skeleton, which is used in the identification of CATs. The two
hydrogen atoms eliminated during the
dehydration of
cathinone (primary
amine) and
methcathinone (secondary
amine) were determined, and the reaction mechanism was elucidated through the
deuterium labeling experiments. The
hydrogen atom bonded to the
amine nitrogen was eliminated with the
proton added during ESI, in both of the tested compounds. This provided evidence that CATs with tertiary
amine structures (such as dimethylcathinone and α-pyrrolidinophenones [α-PPs]) do not undergo
dehydration. However, it was shown that the two major tertiary
amine metabolites (1-OH and 2″-oxo) of CATs generate dehydrated
ions in ESI-CID. The
dehydration mechanisms of the metabolites of α-pyrrolidinobutiophenone (α-PBP) belongs to α-PPs were also investigated. Stable-
isotope labeling showed the
dehydration of the 1-OH metabolite following a simple mechanism where the hydroxy group was eliminated together with the
proton added during ESI. In contrast, the
dehydration mechanism of the 2″-oxo metabolite involved
hydrogen atoms in three or more locations along with the carbonyl group
oxygen, indicating that
dehydration occurred via multiple mechanisms likely including the rearrangement reaction of
hydrogen atoms. These findings presented herein indicate that the dehydrated
ions in ESI-CID can be used for the structural identification of CATs.