Assay of residual organic solvents in topiramate drug substance by capillary gas chromatography.

ABSTRACT

The analysis of residual organic solvents (methanol, ethanol and toluene) in topiramate drug substance was investigated. Topiramate is a potent anticonvulsant drug under clinical evaluation. The drug is recrystallized from ethanol denatured by either methanol or toluene, and each residual solvent is controlled at 0.1% (w/w) level. A capillary gas chromatography (GC) method described in this manuscript utilizes a DB-WAX, 1 micron thick, 30 m x 0.53 mm i.d., column. Since topiramate is a thermally labile compound, the selection of the proper injector temperature is critical to the success of the analysis. The injector temperature 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 11 min. Helium was used as a carrier gas. The sample solvent selected was 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 showed excellent recovery.