A simple and sensitive LC-MS/MS method for determination and quantification of potential genotoxic impurities in the ceritinib active pharmaceutical ingredient

摘要

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for quantification of four potential genotoxic impurities (PGIs) in the ceritinib active pharmaceutical ingredient. Chromatographic separation was achieved using a YMC-Triart C18 column, with 0.1% formic acid in water as mobile phase A and acetonitrile as mobile phase B in gradient elution mode at a 0.5 mL min(-1)flow rate. Quantification of impurities was carried out using triple quadrupole mass detection with electrospray ionization in multiple reaction monitoring mode. The method was fully validated with good linearity over the concentration range of 0.5-5.0 ppm of the ceritinib test concentration for all four PGIs. The correlation coefficient obtained in each case was >0.998. The recoveries were found satisfactory over the range between 83.7 and 107.3% for all selected impurities. The developed method was able to quantitate all four PGIs at a concentration level of 1 ng mL(-1)(0.5 ppm with respect to 2 mg mL(-1)ceritinib).