Identification of novel fragmentation pathways and fragment ion structures in the tandem mass spectra of protonated synthetic cathinones

Abstract

The expanding use of emerging synthetic drugs such as synthetic cathinones, or “bath salts”, is a growing public health concern and a continual challenge for drug analysts. In the tandem mass spectra of protonated α-pyrrolidinophenone cathinones, the tropylium ion at m/z 91 is often among the most abundant product ions, but its mechanistic origin is currently unexplained. This project combined electrospray ionization multi-stage mass spectrometry (ESI-MSn), high-resolution mass spectrometry (HRMS), isotopic labeling and ion spectroscopy to enhance our understanding of the fragmentation pathways and mechanisms of a variety of α-pyrrolidinophenone cathinones. The fragmentation trends derived from these ESI-MS/MS studies are: 1) unlike N-alkylated cathinones, abundant radical cations are not observed from even-electron precursors of α-pyrrolidinophenones; 2) the loss of a 71 Da pyrrolidine neutral to form an alkylphenone cation is always observed; 3) a series of neutral alkenes are lost from the alkylphenone cation to form intermediate cations with phthalane-like structures. The phthalane intermediates then eliminate the carbonyl carbon as CO or C2H2O to form a tropylium ion at m/z 91. The α-carbon of the original cathinone is almost exclusively retained in the tropylium ion. If the original cathinone is substituted on the aromatic ring, the observed tropylium ion will be shifted by the mass of the substitution. These findings explain the characteristic ions in ESI-MS/MS spectra of synthetic cathinones and will help analysts better employ mass spectral observations in future casework.