Development and Validation of a Robust Analytical Method for the Quantification of NDMA and NDEA Impurities in Ranitidine Hydrochloride API by HPLC and LC-MS/MS
DOI:
https://doi.org/10.64149/J.Carcinog.24.3.778-790Keywords:
NDMA, NDEA, Nitrosamine, Ranitidine HCl, LC-MS/MS, HPLC, Method validation, Impurity quantification.Abstract
The detection of N- nitrosodimethylamine (NDMA) and N- nitrosodiethylamine (NDEA), classified as probable human carcinogens, has raised serious safety concerns regarding ranitidine hydrochloride (HCl), a widely used H2-receptor antagonist. This study focuses on the development and validation of sensitive and robust analytical methods using high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of NDMA and NDEA in ranitidine hydrochloride active pharmaceutical ingredient (API). A reversed-phase HPLC method was optimized for preliminary screening, followed by LC-MS/MS for confirmatory quantification. Validation parameters such as specificity, linearity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ) were evaluated as per ICH Q2 (R1) guidelines. The LC-MS/MS method achieved LOD as low as 0.25ng/ml for NDMA and 0.5ng/ml for NDEA. The proposed method is highly suitable for routine ranitidine API quality control analysis and can be extended to related nitrosamine investigations.
