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


METHODS
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.


RESULTS
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.


CONCLUSIONS
A simplified kinetic scheme could be used to describe the concentration-time profiles of 1, the intermediates and the final product.
Riley
C M
CM
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045-2504, USA.
Mummert
M A
MA
Zhou
J
J
Schowen
R L
RL
Vander Velde
D G
DG
Morton
M D
MD
Slavik
M
M
D001380:Azauridine / Q000031:analogs & derivatives* / Q000737:chemistry; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D011355:Prodrugs / Q000737:chemistry*; D012996:Solutions; D013696:Temperature; D013816:Thermodynamics; D014867:Water
D011355:Prodrugs; D012996:Solutions; D014867:Water; D001380:Azauridine; C100231:azaribine