The objective of the present research work is to develop a suitable LC-MS/MS method for the quantitative determination of genotoxic alkylating impurity 2-butyl p-toluenesulfonate present in naproxen drug substance at ppm level. The LC-MS/MS method was developed on Xterra MS C18 50 mm column using the mobile phase consists a mixture of 10 mM ammonium acetate and acetonirile using a isocratic composition of 20:80 v/v. Ion source is electrospray ionization (ESI) positive mode, source temperature is 300 oC, gas flow is 10 L/min, Nebuliser pressure is 50 psi, capillary voltage is 4000 V. Under these LC and MS conditions 2-butyl p-toluenesulfonate was quantified by selected ion mode (SIM) of 173. The limit of detection and the limit of quantitation for the impurity were established. This method has been tested in a number of naproxen samples and used successfully for quantification of the genotoxic impurity at ppm level. Validation of the developed LC-MS/MS method was carried out as per ICH requirements and the data shows that the proposed method is specific, linear, accurate, precise and robust. The developed LC-MS/MS method was found to be suitable to quantify the genotoxic impurity at ppm level present in naproxen drug substance.
Genotoxic impurity, Alkylating agent, LCMS, Electro spray ionization, Atmospheric chemical ionization