Identification and Validation of Potential Genotoxic Impurities, 1,3-Dichloro-2-Propanol, and 2,3-Dichloro-1-Propanol, at subtle levels in bile acid sequestrant, Colesevelam Hydrochloride using hyphenated GC-MS technique

Biomed Chromatogr. 2022 Oct 17:e5528. doi: 10.1002/bmc.5528. Online ahead of print.ABSTRACTPotential Genotoxic Impurities (PGI) and N-nitrosamine impurities in APIs and their determination at the low level are substantial challenges for Cholesterol-lowering agents in recent years. Herein we developed a robust, reliable, rapid, accurate, and validated technique of Gas Chromatography equipped with a Mass Spectrometer (GC-MS) for quantifying subtle levels of 1,3-Dichloro-2-Propanol (PGI-I) and 2,3-Dichloro-1-Propanols (PGI-II) in Colesevelam Hydrochloride drug substance (bile acid sequestrant). The separation of Colesevelam Hydrochloride, PGI-I, and PGI-II were executed with chromatographic technique using Capillary column, DB-624 measuring with 30m x 0.32mm x 1.8μm specification of 6% cyanopropylphenyl-94% dimethylpolysiloxane copolymer and Helium carrier gas. This developed technique gave a good intensity peak without any interference and extra masses at the retention time of 11.17 min for PGI-I and 11.59 min for PGI-II, adequate with the Mass spectrum (m/z) of 79 and 62, respectively. The Method's sensitivity and linearity are demonstrated by its detection and quantification limits at subtle levels with a correlation coefficient of 0.9965 for PGI-I and 0.9910 for PGI-II. The determination is mainly focused on improving sensitivity with LOD and LOQ much below the specifications, which can support the tighter limit. This results in a cost-effective and easily adoptable methodo...
Source: Biomedical Chromatography : BMC - Category: Biomedical Science Authors: Source Type: research