Simultaneous Estimation of Six Nitrosamine Impurities in Valsartan Using Liquid Chromatographic Method.

BACKGROUND: Nitrosamine impurities are potent carcinogens in animals and probable carcinogens in humans. There is a need for effective analytical methods to detect and identify various nitrosamine impurities, and to develop rapid solutions to ensure the safety and quality of the drugs. OBJECTIVE: A liquid chromatographic method was developed for estimation of six nitrosamine impurities in valsartan. METHODS: The developed method employed: a C18 (250 × 4.6 mm, 5 µm) column as a stationary phase; a combination of acetonitrile, water (pH 3.2 adjusted with formic acid), and methanol with gradient elution as mobile phase; and 228 nm as the detection wavelength. The developed method was validated as per International Conference on Harmonization Q2(R1) guidelines. The method was successfully applied to estimate six nitrosamine impurities in valsartan API (active pharmaceutical ingradient) and formulation (tablets). RESULTS: The method was able to separate each impurity and valsartan with resolved and sharp peaks. Results indicated that the developed method is linear in selected ranges (coefficient of regressions >0.9996), precise (RSD <2%), accurate (recovery in a range of 99.02-100.16%), sensitive (low detection and quantitation limits), and specific for estimation of each impurity in valsartan. Assay results were in agreement with the spiked amount of each impurity. CONCLUSION: The developed method can be applied for simultaneous estimation of six nitrosamine impurities in valsartan raw material, tablets, and fixed dose combination at very low levels. HIGHLIGHTS: Development, validation, and application of a HPLC method for the estimation of six nitrosamine impurities in valsartan API and formulation samples.

A decennary update on applications of metal nanoparticles (MNPs) in the synthesis of nitrogen- and oxygen-containing heterocyclic scaffolds.

Heterocycles have been found to be of much importance as several nitrogen- and oxygen-containing heterocycle compounds exist amongst the various USFDA-approved drugs. Because of the advancement of nanotechnology, nanocatalysis has found abundant applications in the synthesis of heterocyclic compounds. Numerous nanoparticles (NPs) have been utilized for several organic transformations, which led us to make dedicated efforts for the complete coverage of applications of metal nanoparticles (MNPs) in the synthesis of heterocyclic scaffolds reported from 2010 to 2019. Our emphasize during the coverage of catalyzed reactions of the various MNPs such as Ag, Au, Co, Cu, Fe, Ni, Pd, Pt, Rh, Ru, Si, Ti, and Zn has not only been on nanoparticles catalyzed synthetic transformations for the synthesis of heterocyclic scaffolds, but also provide an inherent framework for the reader to select a suitable catalytic system of interest for the synthesis of desired heterocyclic scaffold.