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.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/chemistry , Azirines/isolation & purification , Drug Contamination , Phenanthridines/isolation & purification , Photolysis , Tetrazoles/chemistry , Tetrazoles/isolation & purification , Valine/analogs & derivatives , Angiotensin II Type 1 Receptor Blockers/radiation effects , Angiotensin II Type 1 Receptor Blockers/standards , Chromatography, High Pressure Liquid/instrumentation , Chromatography, High Pressure Liquid/methods , Drug Stability , Magnetic Resonance Spectroscopy/instrumentation , Magnetic Resonance Spectroscopy/methods , Molecular Structure , Spectroscopy, Fourier Transform Infrared/instrumentation , Spectroscopy, Fourier Transform Infrared/methods , Tetrazoles/radiation effects , Tetrazoles/standards , Valine/chemistry , Valine/radiation effects , Valine/standards , ValsartanABSTRACT
Following a hypertension symposium in Baltimore, MD, on June 1, 2005, Dr. Wendy Post from the Johns Hopkins University School of Medicine, Baltimore, MD, had the opportunity to interview two of the outstanding hypertension experts in the United States on several controversial issues in hypertension management. Dr. Norman Kaplan is Clinical Professor of Medicine at the Southwestern Health Science Center in Dallas, TX, and Dr. Marvin Moser is Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT. Both have been leaders in the field of hypertension treatment and education for more than 40 years. Dr. Kaplan's book Clinical Hypertension has been a standard textbook since 1973 and is now in its ninth edition. Dr. Marvin Moser was the Senior Medical Consultant to the National High Blood Pressure Education Program from 1974 to 2002 and was Chairman of the first Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure and a member of the six subsequent committees. His book Clinical Management of Hypertension is in its seventh edition. Drs. Moser and Kaplan were corecipients of the 2004 International Society of Hypertension Award for Outstanding Contributions to Hypertension Treatment and Education and have lectured extensively throughout the United States and overseas.
