Isolation and Identification of Process Impurities in Crude Valsartan by HPLC, Mass Spectrometry, and Nuclear Magnetic Resonance Spectroscopy

Abstract

Three unknown recurring impurities were isolated from crude valsartan by a combination of analytical and preparative liquid chromatography. One of the impurities was identified as (S)‐N‐valeryl‐N‐{[2′‐(1‐methyl‐tetrazol‐5‐yl) biphenyl‐4‐yl]‐methyl}‐valine by mass spectrometry and nuclear magnetic resonance spectroscopy. The tentative mechanism for the formation of the impurities is also discussed.

Keywords:

• Valsartan
• Impurities
• Liquid chromatography
• Electrospray ionization mass spectrometry
• Nuclear magnetic resonance spectroscopy
• Degradation

Acknowledgments

The authors wish to thank Researcher Xiaopeng Liu in Huazhong Normal University and Professor Chen in Wuhan University for their help in NMR test. Thank Professor Youjie Zhang for his help in NMR spectra analysis. And thank Associate Professor Zongwei Cai for his help in MS test.