Nitrosamine impurities are potential carcinogens, which are forming from the synthesis of drug substance as byproduct and also forming in presence of NaNO2/HNO3 and secondary amines (e.g., dimethyl amines, diethyl amine etc.,), which should be controlled in the medication of the human beings. Hence, robust and sensitive analytical method is required to control the nitroso amine impurities in drugs. The object of this method is to quantify the N-Nitrosodimethylamine (NDMA) impurity at 0.01 ppm level in ranitidine drug substance (form-1 and form-2) and drug product (tablets and capsules) of different geography. The source of NDMA impurity is also from the dimethyl amine as a key starting material using the ranitidine synthetic process. NDMA is forming when dimethyl amine is reacting with nitrous acid. The optimized LC method conditions were ACE C18-AR 3 µm, 150 × 4.6 mm column, mobile phase A as 0.1% formic acid in water, mobile phase B as 100% methanol, 0.8 ml/minute flow with gradient (time/%mobile phase B): 0/3, 3/3, 15/15, 15.1/100, 17/100, 17.1/3, 22/3, column temperature: 40°C, injection volume 50 µl, and total run time as 22 minutes. The final response achieved with multiple reaction monitoring (MRM) type: MRM [Q1 Mass (Da):75 Q3:58.2 Time (msecond)] in atmospheric chemical ionization positive mode. The optimized method was validated against the International Council for Harmonisation Q2 (R1) and United States of Pharmacopeia general chapter for compendial method validations 1225. This method can detect up to 0.01 ppm and quantify up to 0.03 ppm, the method shows linearity from 0.03 to 20 ppm.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.