Isolation and Characterization of Novel Degradation Products of Valsartan by NMR and High Resolution Mass Spectroscopy: Development and Validation of Valsartan by UPLC

Kasani Kumaraswamy1,2, Hima Bindu Gandham2, Rudrakshula J.D. Prasad1, B. Amarender Reddy1, Muralidharan Kaliyaperumal1 and Chidananda Swamy Rumalla1,*

1Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., IDA Mallapur, Hyderabad-500076, India

2Department of Engineering Chemistry, Andhra University, Visakhapatnam-530003, India

*Corresponding author: E-mail: chidanand_swamy@yahoo.co.in

Abstract

Valsartan is used to treat high blood pressure, heart failure and diabetic kidney disease. It was subjected to forced degradation under acidic, basic and peroxide mediated oxidation. The forced degradation was performed according to ICH guidelines Q1A(R2)−Stability Testing of New Drug Substances and Products. The drug was inert under peroxide mediated hydrolysis, two degradants (DP-Val-1, DP-Val-2) were formed in base hydrolysis and one degradant (DP-Val-3) was formed in acid hydrolysis. These degradants were initially identified through LC-MS and isolated by mass mediated purification system. DP-Val-1 and DP-Val-3 are already reported but their structures were not confirmed by 2D NMR studies. DP-Val-2 is novel degradant and its structure has been elucidated by substantial analysis of high resolution mass spectrometry and 1D, 2D NMR spectroscopy. DP-Val-1 consists of a mixture of rotamers and this hypothesis was confirmed by variable temperature NMR (VT-NMR). A stability indicating RP-UPLC method was developed and validated for assay determination valsartan API drug. A valsartan UPLC method was validated on Acquity BEH C-18 2.1 × 100 mm, 1.7 μm column with shorter runtime of 6 min and the method was validated as per regulatory guidelines in terms of specificity, accuracy, linearity, precision, limit of detection and limit of quantitation.

Keywords

Valsartan, Degradation products, UPLC method.

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