Infinite enantiomeric resolution of basic compounds using highly sulfated cyclodextrin as chiral selector in capillary electrophoresis

Abstract

Four chiral basic analytes, namely methadone, fluoxetine, venlafaxine, and tramadol, were selected as model compounds for investigating their stereoselective separation with highly sulfated gamma-cyclodextrin (HS gamma-CD) by capillary electrophoresis (CE)-UV and CE-mass spectrometry (MS). At high concentration of chiral selector, the preferentially bonded enantiomer migrated faster in the anodic mode to the detector and high resolutions were obtained for all analytes. In the cathodic mode, at lower highly sulphated cyclodextrin (HS-CD) concentration, basic compounds could be detected, with the weakly bonded enantiomer migrating first (enantiomeric migration order inversion). It was also then possible, at intermediate HS-CD concentration, that only one enantiomer migrated to the detector as cation while the other enantiomer complexed with the CD was negatively charged and presented an opposite mobility. The latter never reached the detector achieving a perfect enantiomeric selectivity. Infinite chiral resolutions were thus achieved by CE-UV as well as by CE-electrospray ionisation (ESI)-MS where concentrations of HS-CD were adapted according to the negative contribution of the nebulization gas pressure of the interface.

Enhanced method performances for conventional and chiral CE‐ESI/MS analyses in plasma

“…For this purpose, HS-CD are particularly adapted for basic drug enantioseparation [12,18,43,[62][63][64]. Recently, the possibility to obtain rapid stereoselective analysis (,10 min) of amphetamine derivatives in plasma samples after a simple LLE and an HD injection was demonstrated.…”

Sensitive chiral analysis by capillary electrophoresis

“…The works included in this table are those in which the lowest LODs were obtained. MS detection has been employed in other works on chiral analysis by CE but LODs close to or above 10 25 M were generally obtained [125][126][127][128][129][130][131][132][133]. The basic instrumentation in CE-MS [134] allows, once the electrophoretic separation is performed, the introduction of the analytes in the mass spectrometer using an interface, usually a sheath liquid interface, which enables the establishment of the electrical contact and the nebulization of the solution.…”

Fast chiral separation of drugs using columns packed with sub‐2 μm particles and ultra‐high pressure

“…As LC remains the most widely used technique in the pharmaceutical industry, the discussion will be limited to this approach even if capillary electrophoresis presents some obvious advantages for fast enantioseparations. [9][10][11][12] In 2003, monolithic supports were coated with a chiral selector to perform fast enantioseparations. This material presents some interesting characteristics related to its bimodal structure of macropores and mesopores.…”