Cost-effective, green HPLC determination of losartan, valsartan and their nitrosodiethylamine impurity: application to pharmaceutical dosage forms

Abstract

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.

Microscale thermophoresis as a powerful growing analytical technique for the investigation of biomolecular interaction and the determination of binding parameters

“…MST succeeds to work in presence of micelles and detergents which hinders the aggregation of proteins. Moreover, MST has the advantage of low sample consumption, which agrees to green analytical chemistry concepts [116,117].…”

Design of an Experimental Study for the Simultaneous Determination of Cefepime, Piperacillin and Tazobactam Using Micellar Organic Solvent-Free HPLC

“…The evaluation of greenness of the analytical procedures became of absolute importance in order to minimize the amount of hazardous reagents waste. For instance, a conventional HPLC system can generate up to 0.5 L of organic solvents daily [26]. Therefore, several metrics were developed within the past decade for assessing the impact of analytical procedures on the environment.…”