초록
<P><B>Abstract</B></P><P>Potential genotoxic impurities (PGI) and <I>N</I>‐nitrosamine impurities in active pharmaceutical ingredients (APIs) and their determination at low levels 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‐propanol (PGI‐II) in colesevelam hydrochloride drug substance (bile acid sequestrant). The separation of colesevelam hydrochloride, PGI‐I and PGI‐II was executed with chromatographic technique using a capillary column, DB‐624 measuring with 30 m × 0.32 mm × 1.8 μm 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 times of 11.17 min for PGI‐I and 11.59 min for PGI‐II, which was adequate, with mass spectra (<I>m</I>/<I>z</I>) of 79 and 62, respectively. The method’s sensitivity and linearity are demonstrated by its detection and quantification limits at subtle levels with correlation coefficients of 0.9965 for PGI‐I and 0.9910 for PGI‐II. The determination is mainly focused on improving sensitivity with the limits of detection and quantitation far below the specifications, which can support tighter limits. This results in a cost‐effective and easily adoptable methodology having precise and accurate results in colesevelam hydrochloride API at subtle levels.</P>