Analytical method validation for related substances in sodium valproate oral solution by gas chromatography

Abstract

Abstract Background Sodium Valproate is the sodium salt of valproic acid (VPA). Valproic acid is mainly used for the treatment of epilepsy. The specific aim of the study is to develop and validate an optimized method for the determination of six related substances such as N,N-dimethyl valpronamide, valeric acid, 2-methyl valeric acid, 2-ethyl valeric acid, 2-isopropyl valeric acid and 2-n-butyl valeric acid in Sodium Valproate Oral Solution by Gas Chromatography. Chromatographic separations of these six related substances were achieved on DB-FFAP fused silica capillary column (30 m × 0.53 mm) bonded with a 0.5-µm layer of macrogol 20,000 2-nitroterephthalate materials used as stationary phase. The six related impurities were extracted using heptane and monitored by Gas Chromatography coupled with flame ionization detector. The performance of the developed method was assessed by evaluating system suitability, method precision, specificity, linearity and range, ruggedness, accuracy, robustness. Results The correlation coefficient was within the acceptance criteria in the range of 0.9998. The evaluated concentrations for Sodium Valproate were in the ranges of 5.05–25.27 ppm. The average recovery values were in the range of 92.4–100.4%. Solution Stability experiments were performed to evaluate the degradation behavior of SVS. Conclusion A novel, precise and sensitive GC method was developed, validated and optimized for the determination of six related substances in sodium Valproate oral solution. The results obtained from the validation experiments demonstrated that the method is accurate, precise, linear, specific, sensitive and robust. Hence, the proposed method can be an alternative method, for the determination of related substances in sodium valproate oral solution drug substance.