Angiotensin-converting enzyme inhibitors are one of the most widely used anti-hypertensive drugs which are used to reduce hypertension. In 2018, the United States Food and Drug Administration together with the European Medicine Agency declared the presence of carcinogenic nitrosamine impurities such as nitrosodiethylamine (NDEA) in some of the products, including valsartan (VLS) and losartan (LOS), and drugs' recall procedures were started. Thus, they should be controlled to be below the acceptable cancer risk level to ensure safety of the pharmaceutical products. Therefore, sensitive and reliable analytical methods were required for detection and quantitation of NDEA in bulk and finished drug products. Green analytical chemistry has received great interest to minimize the amount of organic solvents consumed without loss in chromatographic performance. A green and sensitive HPLC method was developed for the determination of NDEA in LOS and VLS using mobile phase of 0.02 M ammonium acetate adjusted to pH 7.2 and ethanol in gradient manner. Limits of detection and limits of quantification for NDEA were estimated to be 0.2 and 0.5 µg ml-1, respectively. The standardized limits of NDEA impurity in drug substances were set as 0.56 ppm, which indicates the feasibility of its determination by the proposed conventional method without need for expensive instrumentations (e.g. MS/MS detectors) that are not found in most pharmaceutical quality control laboratories.
Keywords: green chromatography; losartan; nitrosodiethylamine; process-related impurities; valsartan.
© 2022 The Authors.