Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Small molecules with polar functional groups, including substituted phenethylamines, are commonly analyzed by liquid chromatography‐mass spectrometry (LC‐MS) with electrospray ionization (ESI). Analyte molecules are mostly detected in protonated and cation‐adducted forms through positive‐ion electrospray ionization‐mass spectrometry (ESI‐MS). However, the ESI of substituted phenethylamines commonly provides an intense signal of fragment ions by ESI in‐source collision‐induced dissociation (IS‐CID), which hinders the unambiguous identification of phenethylamines. This phenomenon was approximated as a unimolecular dissociation model, and the dissociation efficiency was evaluated by various quantum chemistry calculations to determine the ESI IS‐CID efficiency. The calculated results were consistent with the experimental data, when the dissociation threshold energy of phenethylamines was calculated using the post‐Hartree‐Fock (post‐HF) method, CCSD(t)/cc‐pVTZ//MP2(full)/6‐311++G(d,p). In contrast to post‐HF methods, the utilization of density functional theory calculations with a suitable functional is recognized as an accurate and competitive low‐cost approach. In particular, ωB97‐XD, M06‐2X‐D3, and recently developed Minnesota functionals, such as M11, MN12‐SX, and MN15, provided reliable results, as in the case of the post‐HF method. The results obtained by the recently developed double hybrid functionals, DSD‐PEBP86‐D3(BJ), PBE0‐DH, and PBE‐QIDH, were also reliable. The consideration of ESI IS‐CID can facilitate the identification of analyte molecules because most phenethylamines, except for <jats:italic>N</jats:italic>‐methylated analogs, provide an intense signal in the ESI mass spectrum.</jats:p>