Development of an analytical method for the determination and quantification of n-nitrosodimethylamine in olmesartan by HPLC-MS/MS

In this study, a simple, rapid, and highly sensitive analytical method has been developed and validated for the detection, separation, and quantification of N-nitrosodimethylamine in the active pharmaceutical ingredient olmesartan medoxomil, as well as in manufactured tablets and marketed tablets, using high-performance liquid chromatography-mass spectrometry. Chromatographic separation was achieved using the Agilent Eclipse XDB-C18 column (5 m × 4.6 mm × 150 mm) with a binary gradient with water as mobile phase A and 0.1 % formic acid in methanol as mobile phase B, flow rate 0.5 mL/min, B. Due to the presence of polar groups, N-nitrosodimethylamine is successfully ionized and quantified in positive atmospheric pressure chemical ionization mode using multiple reaction monitoring. The method was validated according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines, evaluating the limit of detection and quantification, a good signal-to-noise ratio, and an excellent regression coefficient greater than 0.995 were found. The accuracy (expressed as recovery) of the method was performed in triplicate obtaining satisfactory results between 80 and 104 %, with a precision (%RSD) of 0.34 – 1.50 %. The method can be used routinely for the determination and quantification of N-nitrosodimethylamine in olmesartan.