Hydrolysis of the prodrug, 2',3',5'-triacetyl-6-azauridine

• Published in: Pharmaceutical research 1995-09, Vol.12 (9), p.1361-1370
• Main Authors: RILEY, C. M, MUMMERT, M. A, ZHOU, J, SCHOWEN, R. L, VANDER VELDE, D. G, MORTON, M. D, SLAVIK, M
• Format: Article
• Language: English
• Subjects: Azauridine - analogs & derivatives; Azauridine - chemistry; Biological and medical sciences; Drug Stability; Hydrogen-Ion Concentration; Hydrolysis; In Vitro Techniques; Kinetics; Medical sciences; Models, Chemical; Molecular Structure; Pharmacology. Drug treatments; Prodrugs - chemistry; Skin, nail, hair, dermoskeleton; Solutions; Temperature; Thermodynamics; Water
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1016238110533

The purposes were to study the kinetics of hydrolysis of 2',3',5'-triacetyl-6-azauridine (1) in aqueous solution (mu = 0.5) and to identify the main intermediates and products of the reaction. A stability indicating isocratic LC assay was used to study the rate of degradation of 1. A gradient LC assay was used to study the time courses of the degradants. The products of hydrolysis were isolated by preparative liquid chromatography and identified by 1H-NMR and CI-MS. The pKa value was obtained by potentiometric titration. At 36.8 degrees C, the pH-rate profile of 1 in water was adequately described by a four-term rate equation. The intermediates were identified as the primary and secondary di-acetates, and the primary and secondary mono-acetates. The final product was 6-azauridine. A simplified kinetic scheme could be used to describe the concentration-time profiles of 1, the intermediates and the final product.