Characterization of two new potential impurities of Valsartan obtained under photodegradation stress condition

Romina M Bianchini; Patricia M Castellano; Teodoro S Kaufman

doi:10.1016/j.jpba.2011.04.017

Characterization of two new potential impurities of Valsartan obtained under photodegradation stress condition

J Pharm Biomed Anal. 2011 Aug 25;56(1):16-22. doi: 10.1016/j.jpba.2011.04.017. Epub 2011 Apr 27.

Authors

Romina M Bianchini¹, Patricia M Castellano, Teodoro S Kaufman

Affiliation

¹ Pharmaceutical Analysis, Department of Organic Chemistry, School of Pharmaceutical and Biochemical Sciences, National University of Rosario and Institute of Chemistry of Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario (S2002LRK), Argentina.

PMID: 21592713
DOI: 10.1016/j.jpba.2011.04.017

Abstract

A photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV-vis radiation (λ > 320 nm) yielded two previously unknown compounds, which were detected by HPLC. Preparative amounts of the new potential degradation products (DP-1 and DP-2) were obtained by submitting VAL bulk drug to extensive photodegradation. The impurities were isolated by preparative normal phase column chromatography. Analytical information from the infrared, nuclear magnetic resonance and mass spectral data of the degradation products revealed their structures as N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-N-isobutylpentanamide (DP-1) and N-(diazirino[1,3-f]phenanthridin-4-ylmethyl)-N-isobutylpentanamide (DP-2). DP-1 arose from decarboxylation of VAL, while DP-2 results from further loss of nitrogen from the tetrazole motif of DP-1, with concomitant cyclization to yield a tetracyclic diazacyclopropene derivative.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin II Type 1 Receptor Blockers / chemistry*
Angiotensin II Type 1 Receptor Blockers / radiation effects
Angiotensin II Type 1 Receptor Blockers / standards
Azirines / isolation & purification*
Chromatography, High Pressure Liquid / instrumentation
Chromatography, High Pressure Liquid / methods
Drug Contamination*
Drug Stability
Magnetic Resonance Spectroscopy / instrumentation
Magnetic Resonance Spectroscopy / methods
Molecular Structure
Phenanthridines / isolation & purification*
Photolysis*
Spectroscopy, Fourier Transform Infrared / instrumentation
Spectroscopy, Fourier Transform Infrared / methods
Tetrazoles / chemistry*
Tetrazoles / isolation & purification*
Tetrazoles / radiation effects
Tetrazoles / standards
Valine / analogs & derivatives*
Valine / chemistry
Valine / radiation effects
Valine / standards
Valsartan

Substances

Angiotensin II Type 1 Receptor Blockers
Azirines
N-(2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl)-N-isobutylpentanamide
N-(diazirino(1,3-f)phenanthridin-4-ylmethyl)-N-isobutylpentanamide
Phenanthridines
Tetrazoles
Valsartan
Valine