Quantification of potential genotoxic impurity in Divalproex sodium drug substance by GC-MS method.

A sensitive rapid Gas Chromatography with mass spectrometry (GC-MS) method has been developed and validated for the determination of 1-Bromopropane content in Divalproex sodium drug substance. 1-Bromopropane has been considered as a potential genotoxic impurity. The lower level of detection was achieved on fused silica capillary column coated with 100% dimethylpolysiloxane stationary phase with Electron Impact ionization (EI) in Selective Ion Monitoring (SIM) mode. GC runtime was 25min employing programmed temperature with split mode using head-space injection technique. The developed method was validated for specificity, linearity, accuracy and precision. The detection and quantitation limits of 1-Bromopropane obtained were 0.05 μg/g and 0.10 μg/g respectively. The method was found to be linear in the range between 0.10 μg/g and 0.75 μg/g with correlation coefficient 0.9999. The average recovery obtained in Divalproex sodium drug substance was 97.3%. The developed method was found to be rugged for the determination of 1-Bromopropane in divalproex sodium drug substance. The detailed approach of experiments is discussed in the paper