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

ABSTRACT

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.