The detection and quantification of potential genotoxic impurities (PGIs) play an important role in the pharmaceutical industry. The industry needs highly selective and sensitive analytical methods for trace level quantification of these PGIs in drug substances. A sensitive and stability indicating LC-MS/MS method was developed for the simultaneous detection and quantification of (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (ABO) and (S)-4-(4-nitrobenzyl)-1,3-oxazolidin-2-one (NBO) PGIs in zolmitriptan. Method utilizes, Hypersil BDS C18 column (50 mm x 4.6 mm, 3.0 μm) with electrospray ionization in selective ion recording (SIR) mode for quantitation of ABO and NBO PGIs. The method validated as per International Conference on Harmonization (ICH) guidelines and is able to quantitate ABO at 0.1 ppm and NBO at 0.2 ppm with respect to 2.0 mg/mL of zolmitriptan. The method was linear in the range of 0.1-2.0 ppm for ABO and 0.2-2.0 ppm for NBO which matches the range of LOQ-200% of specification level (1.0 ppm). The correlation coef?cient obtained was >0.999 in both the cases. The impurities were not present in the three studied pure and formulation batches of zolmitriptan. The accuracy of the method was ranged between 98.6-102.5% for both ABO and NBO PGIs. The developed method is a good quality control tool to monitor ABO and NBO PGIs in zolmitriptan during its manufacture.
linearity, ICH guidelines, Genotoxicity, Zolmitriptan, LC-MS/MS, Recovery; Stability