Journal of pharmaceutical and biomedical analysis
July 15, 2022
Graeme Cochrane, Jennifer K Field, Matthew C Hulme et al.
9 citations
Supercritical fluid chromatography (SFC) with a carbon dioxide and ammonium acetate gradient separates 31 novel diphenidine-derived psychoactive substances, including regioisomers, in under 10 minutes. Different stationary phases (acidic, neutral, basic) produce medium to large selectivity differences between isomers. Acidic silica phases retain diphenidines longer via electrostatic attraction, while basic phases reduce retention via repulsion. Baseline separation is achieved for six of eight substituted groups on a simple silica column. As halo-substituent size increases, resolution between ortho- and meta-isomers decreases, causing co-elution of ortho- and meta-bromodiphenidines. Elution orders differ from reversed-phase UHPLC, providing orthogonal separation, with hydrophilic compounds better retained on SFC columns.
Journal of pharmaceutical and biomedical analysis
July 15, 2022
Jennifer K Field, Christine Hinz, Christopher M Titman et al.
4 citations
A rapid UHPLC-MS/MS method can detect and confirm 33 different diphenidine derivatives in solid drug samples. The method separates compounds based on the position and type of chemical substituents on the phenyl ring, and it works even when common adulterants are present. The 10-minute protocol was successfully used to identify psychoactive components in four seized drug samples from law enforcement.
Journal of pharmaceutical and biomedical analysis
June 15, 2025
Melvin R Euerby, Benjamin S Barrett, Andrew Costello et al.
A practical HPLC method using six polysaccharide-based chiral stationary phases with a single polar organic solvent mobile phase separated the enantiomers and regioisomers of 32 novel diphenidine-derived psychoactive substances. The cellulose tris(3-chloro-4-methylphenylcarbamate) coated on silica gave baseline separation for 25 of 26 monosubstituted diphenidines with resolution values above 1.5, and optimum separation for 21 of them (resolution 2.9–22.4). The chiral selector type and the substituent position on the 1-phenyl ring strongly influenced chiral resolution, with 4-position substituents showing greater discrimination than 2-position ones. Enantiomer elution order reversed for 2-methoxphenidine depending on the stationary phase. Analysis of real samples confirmed 2-methoxphenidine and diphenidine were traded as racemates, and common adulterants did not interfere.
Acta crystallographica. Section E, Crystallographic communications
March 1, 2025
Ryan E Mewis, Matthew C Hulme, Jack Marron et al.
Five fluorinated diphenidine derivatives were synthesized and their structures determined using NMR spectroscopy and X-ray crystallography. All five compounds form hydrogen bonds between their quaternary amine hydrogen atoms and chloride ions. Two compounds show N-H⋯Cl distances of 2.21–2.31 Å, while three exhibit shorter distances of 2.07–2.20 Å. The compound with a pyrrolidine ring adopts an envelope conformation, and the one with a piperidine ring adopts a chair conformation. Crystal packing in all five structures involves C-H⋯π interactions, and no π-π interactions are observed.