Degradation studies of pentoxifylline: Isolation and characterization of a novel gem-dihydroperoxide derivative as major oxidative degradation product

Pentoxifylline was subjected to various stress conditions and degradation profile was studied with conventional LCMS. Interestingly, under oxidative stress conditions the drug substance underwent distinct transformation to give rise to a single major degradation product. The structure of this produc...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2010-11, Vol.53 (3), p.335-342
Main Authors: Mone, Mahesh Kumar, Chandrasekhar, K.B.
Format: Article
Language:English
Subjects:
Analysis
Analytical, structural and metabolic biochemistry
Biological and medical sciences
Chromatography, High Pressure Liquid
Drug Stability
Fundamental and applied biological sciences. Psychology
gem-Dihydroperoxide
General pharmacology
Magnetic Resonance Spectroscopy
Mass Spectrometry
Medical sciences
Oxidation-Reduction
Oxidative Stress
Pentoxifylline
Pentoxifylline - chemistry
Peroxides - chemistry
Pharmacology. Drug treatments
Stability indicating
Ultra high performance liquid chromatography
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Summary:Pentoxifylline was subjected to various stress conditions and degradation profile was studied with conventional LCMS. Interestingly, under oxidative stress conditions the drug substance underwent distinct transformation to give rise to a single major degradation product. The structure of this product was elucidated using 1D, 2D NMR spectroscopy, high resolution mass spectrometry (Q-TOF LC/MS) and found to be a novel gem-dihydroperoxide, namely 1-(5,5-Bis-hydroperoxy-hexyl)-3,7-dimethyl-3,7-dihydro-purine-2,6-dione. An efficient stability indicating liquid chromatographic separation method was developed for pentoxifylline and its three degradation products (including two from base hydrolysis) using 1.8 μm, C18 reverse phase column and UHPLC. Baseline separation was achieved with a run time of 4 min. The analytical assay method was validated with respect to system suitability, specificity, linearity, range, precision, accuracy and robustness.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2010.04.006