ASSAY OF RESIDUAL ORGANIC-SOLVENTS IN TOPIRAMATE DRUG SUBSTANCE BY CAPILLARY GAS-CHROMATOGRAPHY

The analysis of residual organic solvents (methanol, ethanol and tolue ne) in topiramate drug substance was investigated. Topiramate is a pot ent anticonvulsant drug under clinical evaluation. The drug is recryst allized from ethanol denatured by either methanol or toluene, and each residual solvent is controlled at 0.1% (w/w) level. A capillary gas c hromatography (GC) method described in this manuscript utilizes a DB-W AX, 1 mu m thick, 30 m x 0.53 mm i.d., column. Since topiramate is a t hermally labile compound, the selection of the proper injector tempera ture is critical to the success of the analysis. The injector temperat ure was set at 120 degrees C to prevent degradation. The initial oven temperature was set at 55 degrees C for 8 min and programmed at a rate of 30 degrees C min(-1) to a final temperature of 160 degrees C for 1 1 min. Helium was used as a carrier gas. The sample solvent selected w as dimethylformamide pretreated with molecular sieves to remove trace amounts of alcohols that may interfere with the assay. The method was validated to be specific, linear, precise, sensitive, rugged and showe d excellent recovery.