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%.