Vinyltrimethylsilane Chemical Ionization Tandem Mass Spectrometry Separates Methoxyphenylpiperazine Isomers

Novel synthetic drugs often contain aromatic positional isomers that are difficult to distinguish by conventional mass spectrometry due to similar fragmentation patterns and retention times. Isomers of methoxyphenylpiperazine (MeOPPs) exemplify this analytical challenge. Here, we employed chemical ionization tandem mass spectrometry using vinyltrimethylsilane as the reagent gas to analyze trifluoroacetyl-derivatized MeOPP isomers. This approach generated diagnostic fragment ions unique to the <i>ortho</i>, <i>meta</i>, and <i>para</i> isomers, enabling their unambiguous discrimination in a single analytical run. Density functional theory calculations supported the proposed fragmentation pathways and provided mechanistic insight into the observed isomer-specific selectivity. This straightforward and robust method offers a promising strategy for precise isomer identification in forensic and pharmaceutical contexts where the accurate differentiation of synthetic drug isomers is critical.