Guilty by Dissociation: Part B: Evaluation of Supercritical Fluid Chromatography (SFC-UV) for the analysis of regioisomeric diphenidine-derived Novel Psychoactive Substances (NPS)

Cochrane, Graeme, Field, Jennifer K, Hulme, Matthew C, Gilbert, Nicolas, Mewis, Ryan E, Euerby, Melvin R and Sutcliffe, Oliver ORCID: https://orcid.org/0000-0003-3781-7754 (2022) Guilty by Dissociation: Part B: Evaluation of Supercritical Fluid Chromatography (SFC-UV) for the analysis of regioisomeric diphenidine-derived Novel Psychoactive Substances (NPS). Journal of Pharmaceutical and Biomedical Analysis, 216. p. 114797. ISSN 0731-7085

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Abstract

Supercritical Fluid Chromatography (SFC-UV) employing a carbon dioxide (CO2) and 10 mM ammonium acetate (pH unadjusted) in MeOH-water (95:5 v/v) gradient provides a rapid analysis (tG <10 mins) of 31 novel, regioisomeric diphenidine-derived psychoactive substances, on a range of stationary phases of differing polarity. Medium to large selectivity differences between regioisomers, was observed on the acidic, neutral and basic SFC phases. The greatest selectivity differences were obtained with the acidic and basic phases and the smallest between acidic and neutral phases. For individual substituted ortho-, meta- and para-isomers, the same elution order was observed irrespective of the nature of the stationary phase. This suggested that partitioning into the aqueous layer surrounding the stationary phases as well as the electrostatic interactions between the protonated diphenidine derivatives and the stationary phase, may be the primary retention mechanisms under these SFC conditions. The acidic silica stationary phases yielded longer retention of the analytes via electrostatic attraction, whereas the basic phases resulted in shorter retention via electrostatic repulsion. SFC effected acceptable separation of six of the eight substituted groups of ortho-, meta- and para-diphenidines evaluated. As the size of the halo-substituent increased, the resolution between ortho-/meta-isomers decreased, resulting in co-elution of the ortho- and meta-bromodiphenidines. Fluphenidines and chlorodiphenidines generated an elution order of meta- < ortho- < para- whereas an elution order switch was observed for the iodophenidines. This contrasted with RP-UHPLC where the elution order for the fluphenidines and iodophenidines was para- < ortho- < meta- and para- < meta- < ortho- respectively. An orthogonal elution order of diphenidines was demonstrated between the RP-UHPLC and SFC stationary phases due to the polarity differences between the separation modes. In general, hydrophilic compounds, which were poorly retained on a C18 reverse phase column, were well retained on SFC columns.