Determination of degradation products of squalamine lactate using LC/MS

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 32; no. 1; pp. 85 - 96
• Main Authors: Li, Cong-jun, Prasad Kari, U., Noecker, Lincoln A., Jones, Stephen R., Sabo, Andrew M., McCormick, Timothy J., Johnston, Sean M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 24.04.2003; Elsevier Science
• Subjects: Analysis; Biological and medical sciences; Cholestanols - analysis; Cholestanols - chemistry; Chromatography, Liquid - methods; Degradation; Drug Stability; General pharmacology; Indicators and Reagents; Injections; LC/MS; Mass Spectrometry - methods; Medical sciences; Pharmacology. Drug treatments; Reproducibility of Results; Sensitivity and Specificity; Squalamine; Degradation; LC/MS; Squalamine; Antineoplastic agent; Steroid; Denaturation; Animal origin; Liquid chromatography; Mass spectrometry MS/MS; Antiangiogenic agent; Degradation product; Mass spectrometry; Comparative study; Quantitative analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/S0731-7085(03)00047-5

Heat, acid and base stress methods were applied to study the stability of squalamine lactate. Liquid chromatography coupled with mass spectrometry was used to analyze the degraded samples and tentative structural identifications were assigned based on their molecular weight measurements, reactivity and MS/MS fragmentation. Solid squalamine lactate generated a new amide, namely lactyl squalamide, when heated to 80 °C. Chemical structure for this new compound has been established by NMR and MS data interpretation and confirmed by direct comparison between the degradant and the synthesized compound. Squalamine lactate in pH 4 acetate buffer solution produced more degradants under stressed conditions. These degradants are formed due to the loss of the sulfate functionality. Squalamine lactate is stable in refrigerated conditions as well as in basic solution.