Separation and quantitation of the S-(+)-enantiomer in the bulk drug tiagabine x HCl by chiral high-performance-liquid chromatography using a Chiralcel-OD column.
Tiagabine x HCl is being developed as an anti-convulsant/anti-epileptic agent for seizure disorders. The pharmacological activity of the R-(-)-enantiomer is higher than that of the S-(+)-enantiomer. Therefore, the drug is synthesized in the pure R-(-)-enantiomeric form. The enantiomers of tiagabine x HCl were separated on a modified cellulose stationary phase (Chiralcel-OD) with a mobile phase of hexane-isopropanol-ethanol (80:14:06, v/v/v). Approximately 5 ml of trifluoroacetic acid was added for each liter of the mobile phase mixture. The method is capable of separating the two enantiomers with a selectivity factor of 1.55 and a resolution factor of 3.4. The samples of tiagabine x HCl were monitored by a UV detector at 260 nm. The method was validated by conducting standard addition and recovery of the S-(+)-enantiomer in tiagabine x HCl. The R.S.D. of the method is 3.2%. The limit of quantification (LOQ) of the S-(+)-enantiomer present in tiagabine x HCl is about 0.03%.
Rustum
A M
AM
Department 41G, Bioanalytical Research, Abbott Laboratories, North Chicago, IL 60064, USA.
Estrada
V
V
D000927:Anticonvulsants / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D009557:Nipecotic Acids / Q000032:analysis* / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D000078308:Tiagabine
D000927:Anticonvulsants; D009557:Nipecotic Acids; D000078308:Tiagabine