title: Screening approach, optimisation and scale-up for chiral liquid chromatography of cathinones.
abstract: Screening approaches adopted in pharmaceutical companies for chiral LC method development may be quite complicated and sophisticated in order to guarantee a high success rate. However in other environments it may be of more value to assess how simple a screen might be used to still have a good chance of achieving success. The genuine need to develop chiral separations for the former 'legal-high' drug mephedrone and related cathinones of topical interest presented a good opportunity to develop this theme. In initial work on mephedrone itself, no chiral separation was observed on Chirobiotic V, Cyclobond I 2000 DNP, Whelk-O1 and AmyCoat using reversed phase mobile phases. However, using normal phase solvents, chiral separation was observed on all the chiral stationary phases (CSP) used except Chiralcel OJ-H. Of the chiral separations observed on RegisPack, RegisCell and Whelk-O1, some optimisation work was carried out on the latter two which had showed the greatest enantioselectivity. Following optimisation, the best enantioselectivity (1.59) and enantioresolution (5.90) was found with a 250 mm × 4.6 mm I.D. Whelk-O1 column using a propan-2-ol (IPA)-hexane-trifluoroacetic acid (TFA)-triethylamine (TEA) (10:90:0.05:0.05, v/v/v/v) mobile phase. Subsequent screening on other cathinones was restricted to RegisPack, RegisCell and Whelk-O1 or equivalent phases with two mobile phases and this gave a very good success rate. Indeed it was possible to separate all six cathinones on one column, RegisCell, with one mobile phase, propan-2-ol-hexane-TFA (15:85:0.1, v/v/v) but obviously it had been necessary to go through the 3-column screen to arrive at this finding. While Whelk-O1 was not so successful, ease of optimisation on this phase was again a feature. To illustrate the applicability of these separations, it was shown that, as a basis for semi-preparative work, the optimsed mephedrone separation on Whelk-O1 could be scaled-up to a 2000μl injection of a 1.0 mg ml(-1) solution in mobile phase (2.0mg on-column) while still using the 250 mm × 4.6 mm I.D. analytical column.
authors.affiliation: Sunderland Pharmacy School, Sciences Complex, Dale Building, University of Sunderland, Sunderland SR1 3SD, UK.
authors.forename: R Wimal H
authors.initials: RW
authors.lastname: Perera
authors.forename: Ijeoma
authors.initials: I
authors.lastname: Abraham
authors.forename: Shradha
authors.initials: S
authors.lastname: Gupta
authors.forename: Patrycja
authors.initials: P
authors.lastname: Kowalska
authors.forename: Danielle
authors.initials: D
authors.lastname: Lightsey
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Marathaki
authors.forename: Nagendra S
authors.initials: NS
authors.lastname: Singh
authors.forename: W John
authors.initials: WJ
authors.lastname: Lough
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; C023665:cathinone