Validated GC–APCI–MS/MS Method for Sensitive Determination of N‑Nitrosodimethylamine in Valsartan Hydrochloride

Abstract

The detection of trace-level nitrosamine impurities remains a critical challenge in pharmaceutical analysis, requiring highly selective and reproducible chromatographic and spectroscopic techniques. In this study, we present a validated gas chromatography–atmospheric pressure chemical ionization tandem mass spectrometry (GC–APCI–MS/MS) method for the quantification of N-nitrosodimethylamine (NDMA) in valsartan hydrochloride. The method eliminates pre-concentration steps, enabling rapid high-throughput analysis with a runtime of ~12 minutes. Validation was performed in accordance with ICH Q2(R1) guidelines. The method demonstrated excellent linearity (R² = 0.99985), low detection limit (LOD = 0.045 ppm), quantitation limit (LOQ = 0.090 ppm), and high recovery (90.4–97.5%). Compared with conventional electron ionization (EI) approaches, APCI provided enhanced selectivity and reduced matrix interference. The robustness of the method was confirmed through precision studies across multiple concentration levels, with %RSD values well within acceptance criteria. This work highlights the analytical advantages of GC–APCI–MS/MS for nitrosamine determination and establishes a reliable platform for pharmaceutical quality control, with potential extension to environmental and food safety applications.