A selective and sensitive UPLC-MS/MS approach for trace level quantification of four potential genotoxic impurities in zolmitriptan drug substance

Abstract

The pivotal task of pharmaceutical industry is to separate and quantify the potential genotoxic impurities (PGIs) rising from the process of drug production. For trace level quantification of these PGIs we need to develop sensitive and selective analytical methods. APP, NPA, NPP and MNA have been highlighted as PGIs in zolmitriptan. A sensitive and selective UPLC-MS/MS method has developed for identification and quantification of four PGIs viz. APP, NPA, NPP and MNA in zolmitriptan. The method utilizes Hypersil BDS C8 column (50 mm × 4.6 mm, 3.0 μm) with electrospray ionization in selected ion recording (SIR) mode for quantitation of four PGIs. The method was validated as per International Conference on Harmonization (ICH) guidelines and is able to quantitate APP at 0.1 ppm and NPA, NPP and MNA at 0.15 ppm with respect to 5.0mg/mL of zolmitriptan. The proposed method is specific, linear, accurate and precise. The method is linear in the range of 0.1-2.0 ppm for APP and 0.15-2.0 ppm for NPA, NPP and MNA, which matches the range of LOQ-200% of estimated permitted level (1.0 ppm). The correlation coefficient obtained was >0.999 in each case. The impurities were not present in the studied three pure and formulation batches of zolmitriptan. The accuracy of the method was ranged between 98.1 and 102.8% for four PGIs. This method is a good quality control tool for quantitation of four APP, NPA, NPP and MNA PGIs at very low levels in zolmitriptan.

Keywords: Genotoxicity; Linearity; Solution stability; UPLC–MS/MS; Zolmitriptan.