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

• 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
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2010.04.006

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.