Nonaqueous capillary electrophoresis-mass spectrometry for separation of venlafaxine and its phase I metabolites.
Aqueous and nonaqueous capillary electrophoresis (NACE) were investigated for separation of venlafaxine, a new second-generation antidepressant, and its three phase I metabolites. Working at basic pH, around the venlafaxine pKa value, was effective in resolving the investigated drugs, but created considerable peak tailing. To overcome electrostatic interactions between analytes and silanol groups, investigations were also carried out at acidic pH. However, despite the addition of up to 50% v/v of organic solvents (e.g., methanol or acetonitrile), complete separation of the studied compounds was not possible. NACE was found to be an appropriate alternative to resolve venlafaxine and its metabolites simultaneously. Using a conventional capillary (fused-silica, 64.5 cm length, 50 microm inner diameter), and a methanol-acetonitrile mixture (20/80 v/v) containing 25 mM ammonium formate and 1 M formic acid, complete resolution of these closely related compounds was performed in less than 3.5 min. Selectivity, efficiency and separation time were greatly affected by the organic solvent composition. As the electric current generated in nonaqueous medium was very low, the electric field was further increased by reducing the capillary length. This allowed a baseline resolution of venlafaxine and its three metabolities in 0.7 min. Selectivity was compared in aqueous and nonaqueous media in relation to the acid-base properties of the analytes as well as to the solvation degree. Finally, the method successfully coupled on-line to mass spectrometry with electrospray ionization interface allowed significant sensitivity enhancement.
Laboratory of Pharmaceutical Analytical Chemistry, University of Geneva, Switzerland.
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S
Cherkaoui
S
S
Rudaz
J L
JL
Veuthey
D018687:Antidepressive Agents, Second-Generation / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D003511:Cyclohexanols / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D000069468:Desvenlafaxine Succinate; D019075:Electrophoresis, Capillary / Q000379:methods*; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; C434332:N-desmethylvenlafaxine; D000069470:Venlafaxine Hydrochloride; C434333:N,O-didesmethylvenlafaxine; D000069468:Desvenlafaxine Succinate