Liquid Chromatography–Mass Spectrometry Method for Determination of N‐Methyl‐N‐Nitrosopyridin‐4‐Amine in a Vonoprazan Fumarate Drug

Abstract

ABSTRACTN‐methyl‐N‐nitrosopyridin‐4‐amine (4‐MNPA) was one of the nitrosamine impurities observed in the vonoprazan fumarate (VF) during the production of the VF‐active pharmaceutical ingredient. Therefore, a sensitive and efficient multiple reaction monitoring method has been developed for the quantitative estimation of 4‐MNPA impurity in VF. Good separation of 4‐MNPA and VF was achieved using a Zorbax SB‐phenyl (250 × 4.6 mm2, 5 µm) column under gradient eluent conditions. The mobile phases included 0.005 M ammonium formate and methanol as mobile phases A and B, respectively. The column flow rate was 0.8 mL min−1, and a mixture of methanol and water (50:50, v/v) was used in the present study. The 4‐MNPA method was validated with the limit of detection and limit of quantification concentrations of 0.5 and 1.5 µg mL−1, respectively. The linearity range was covered from 1.5 to 6.0 µg mL−1. The % coefficient of variation for repeatability and intermediate precision results was found to be 2.0% and 2.4%, respectively. The % recovery results were within the range of 70%–130%. In conclusion, the developed method using liquid chromatography–tandem mass spectrometry represents a suitable, linear, precise, and an accurate method for determining the 4‐MNPA impurity in VF.