Abstract

N-nitrosodimethylamine is a carcinogenic agent accidentally found in ranitidine formulations. For the products to be safe for human use and quality control test, the estimation of N-nitrosodimethylamine in ranitidine is significantly important. The goal of this study was to use liquid chromatography with tandem mass spectrometric technique for the development and validation of N-nitrosodimethylamine in ranitidine drug and tablets. The proposed approach was utilized to estimate routine analysis of N-nitrosodimethylamine in ranitidine drug and tablets. The injection volume 20 µl and wavelength 254 nm was selected for N-nitrosodimethylamine and ranitidine quantification. Binary mobile phase in a gradient mode was used for the study. The mixture of solvent A (0.1 % formic acid in water) and solvent B (0.1 % formic acid in methanol) was used as the mobile phase. The flow rate of 0.6 ml/min in gradient mode with complete run time of 14 min was used for the analysis. For N-nitrosodimethylamine analysis multiple reaction monitoring transitions were 75.80/44.20 (quantitative analysis) and 75.80/58.20 (qualitative analysis). N-nitrosodimethylamine retention time (tR) was found at 1.25 min. For N-nitrosodimethylamine, the limit of detection was 0.3 ng/ml and limit of quantitation was found to be 1 ng/ml. The linearity range for N-nitrosodimethylamine was decided as 1, 2, 5, 10, 20 and 50 ng/ml from its intensity response. The regression value observed in a linearity graph was 0.9999. The method was specific (no interference of any peak), validated for its accuracy (98.07 to 100.22±1.7565), precision (98.64 to 99.44±0.9083) and robustness (does not effect on developed method by slight change in flow rate and column temperature). In the validation investigation, the quality control levels lower quality control (4 ng/ml), middle quality control (8 ng/ml) and higher quality control (40 ng/ml) were used. Newly developed and validated method for N-nitrosodimethylamine in ranitidine by liquid chromatography with tandem mass spectrometry was accurate, precise and sensitive. The developed method was further used for routine analysis of N-nitrosodimethylamine in ranitidine drug and tablets.