A novel fast analytical method for the determination of N-nitroso vonoprazan in vonoprazan tablets and raw materials using LC-ESI-MS/MS

Abstract

ABSTRACT The presence of N-nitrosamine contaminants in pharmaceuticals, particularly N-nitroso vonoprazan (NVP), poses significant health risks due to their genotoxic and carcinogenic properties. This study describes a novel, rapid analytical method for detecting and quantifying NVP in vonoprazan tablets and raw materials. The NVP was separated and quantified using an LC-ESI-MS/MS system with ESI ionisation and an Exion LC Sciex 5500-QTrap. The system utilised an ACE 3 C18-PFP column with dimensions of 4.6 mm × 150 mm and 3.0 µm. It achieved a high correlation coefficient (R2 = 0.9955) and met linearity and accuracy criteria. The method was developed and validated using ICH guidelines and against standard solutions, and it demonstrated high precision, accuracy, and specificity. The method validation results showed that the quantification is accurate, with an RSD of less than 10% and LOD and LOQ values of 0.5 and 1.0 ng/mL, respectively. The analysis of 150 vonoprazan tablets and 100 raw material samples revealed low levels of NVP, mostly falling below the FDA’s Acceptable Daily Intake limit of 96 ng/day. This novel approach provides a powerful and dependable tool for ensuring the safety and quality of vonoprazan-based pharmaceuticals.