Identification, development and determination of genotoxic impurities in Colesevelam hydrochloride drug substance using gas chromatography coupled with mass detector

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A selectivity-based gas chromatography coupled with a mass detector (GC–MS) technique was developed and evaluated to detect genotoxic impurities in the “Colesevelam hydrochloride (COLH)” drug substance. A chromatographic separation was performed using an HP-5MS column of 30 m long, 0.32 mm in diameter and 1.0 µm thick. For the determination of Epichlorohydrin, 1,6-Dibromohexane and 1-Bromodecane contents, the mass fragments (m/z) 57, 83 and 135 were selected as quantification ions and the mass fragments (m/z) 49, 55 and 57 were selected as qualifier ions respectively. These compounds are analysed using gas chromatography coupled with electron ionization mass spectrometry (GC-EI-MS) using selective ion monitoring (SIM). This method is specific, sensitive, linear, accurate, precise and robust. The respective limits of detection (LOD) and limits of quantification (LOQ) values for Epichlorohydrin, 1,6-Dibromohexane, and 1-Bromodecane were 0.03 µg/g and 0.10 µg/g, 0.03 µg/g and 0.10 µg/g, and 0.03 µg/g and 0.10 µg/g, respectively.The correlation co-efficient value of the linearity experiment was 0.9995 for Epichlorohydrin, 0.9997 for 1,6-Dibromohexane and 0.9997 for 1-Bromodecane. The average recovery for Epichlorohydrin was 97.0 %, 1,6-Dibromohexane 103.4 % and for 1-Bromodecane was 106.3 %. The present method is precise according to system, method and intermediate precision. These results demonstrate that controlling for Epichlorohydrin, 1,6-Dibromohexane, and 1-Bromodecane in COLH drug substance is both straightforward and economical.