European Journal of Biomedical and Pharmaceutical Sciences

DOVELOPMENT AND VALIDATION OF A HEAD SPACE GAS CHROMATOGRAPHIC METHOD FOR THE DETERMINATION OF NINE ORGANIC VOLATILE IMPURITIES IN TOPIRAMATE API

Mannem Durga Babu and K. Surendra Babu*

ABSTRACT

Objective: Topiramate is an anticonvulsant drug. To provide quality control over the manufacture of any API, it is essential to develop highly selective analytical methods. In the current article we are reporting the development and validation of a rapid and specific head space gas chromatographic (HSGC) method for the determination of nine organic volatile impurities in topiramate API. Methods: The method development and its validation were performed on Shimadzu GC-2010 Gas Chromatographic system equipped with flame ionization detector and teledyne tekmar HT3TM head space analyzer. The method involved a thermal gradient elution of nine organic volatile impurities present in topiramate API. VF-624ms, 60 m × 0.32 mm, 1.0 μ column using nitrogen gas as a carrier. The flow rate was 2.5 ml/min and flame ionization detector (FID) was used. Results: The method was linear for all nine solvents in topiramate LOQ to 200% μg/ml, respectively. The coefficient of correlation (r2) for the all solvents was not less than 0.99. The limit of detection obtained for acetone, IPA, acetonitrile, MDC,n-Hexane, EA, THF, pyridine and toluenewas 0.19, 0.36, 1.01, 0.18, 0.86, 0.22, 0.20, 1.17, 0.19% and the limit of quantification (LOQ) obtained was 0.59, 1.10, 3.05, 0.54, 2.61, 0.66, 0.61, 3.56, 0.58%. The method was fully validated, complying Food and Drug Administration, ICH and European Medicines Agency guidelines. Furthermore, verified precision, accuracy, LOQ precision, LOQ accuracy, ruggedness, and robustness. Conclusion: The method has been successfully applied for the quantification of the amount of Organic Volatile Impurities present in Topiramate API. The method presents a simple and reliable solution for the routine quantitative analysis of Organic Volatile Impurities present in Topiramate API.

Keywords: Acetone, IPA, Acetonitrile, Dichloromethane, n-Hexane, Ethyl acetate, Tetra Hydro Furan, Pyridine, Toluene, Topiramate, Method Validation.