Determination of Genotoxic Impurity N-nitrosovarenicline in Varenicline Tartrate by UPLC-MS/MS

OBJECTIVE To eatablish a ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry(UPLC-MS/MS) method for the detection of genotoxic impurity N-nitrosovarenicline in varenicline tartrate active pharmaceutical ingredients(APIs) and tablets. METHODS The separation was performed on a ACQUITY UPLC^® CSH^TM Phenyl-Hexyl(150 mm×3.0 mm, 1.7 μm) column with the mobile phase consisting of 0.1% formic acid aqueous solution(mobile phase A) and 0.1% formic acid methanol solution(mobile phase B) by gradient elution at flow rate of 0.45 mL·min^-1 and the column temperature was 50℃. Multiple reaction monitoring(MRM) was performed to quantitatively detect genotoxicity impurities on triple quadrupole mass spectrometer equipped with ESI source in positive mode. RESULTS The impurity had a good linear relationshop in the range of 0.10-10.04 ng·mL^-1. The recoveries(n=3) in APIs of low, middle, high adding concentrations were 103.58%(RSD=3.30%), 98.65%(RSD=2.73%), 92.00%(RSD=1.98%), respectively. The recoveries(n=3) in tablets of low, middle, high adding concentrations were 91.53%(RSD=0.78%), 96.76%(RSD=3.12%), 93.01%(RSD=2.21%), respectively. The limit of detection and the limit of quantitation were 0.014 ng·mL^-1, 0.046 ng·mL^-1, respectively. CONCLUSION The method is sensitive, accurate, which is applicable for quantifications of genotoxic impurity N-nitrosovarenicline in varenicline tartrate APIs and tablets, providing technical support for the quality control of varenicline tartrate.