title: Kinetics and mechanism of captopril oxidation in aqueous solution under controlled oxygen partial pressure.
abstract: The stability of captopril in aqueous solution at 32 degrees C was studied in the pH range 6.6 to 8.0 under controlled oxygen partial pressure (90-760 mm Hg) with and without the addition of cupric ion. The oxidation product, captopril disulfide, was found to be the sole degradation product. A change in reaction rate from first order to zero order occurs as the captopril concentration decreases. The concentration at which this transition takes place is a function of the pH, oxygen partial pressure, and cupric ion concentration. The apparent first-order rate constants show a first-order dependency on both the oxygen partial pressure and the cupric ion concentration. However, the apparent zero-order rate constants show a first-order dependency on oxygen partial pressure and a second-order dependency on cupric ion concentration. As the pH increases from 6.6 to 8.0, the first-order process becomes more predominant. A mechanism which consists of cupric ion- and molecular oxygen-catalyzed oxidation is proposed to explain those observations.
authors.affiliation: Stuart Pharmaceuticals, Division of ICI Americas Inc., Wilmington, Delaware 19897.
authors.forename: T Y
authors.initials: TY
authors.lastname: Lee
authors.forename: R E
authors.initials: RE
authors.lastname: Notari
mesh_terms: D002216:Captopril / Q000032:analysis*; D003300:Copper / Q000494:pharmacology; D003505:Cyclodextrins / Q000494:pharmacology; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D010084:Oxidation-Reduction; D010100:Oxygen; D010313:Partial Pressure; D012996:Solutions / Q000032:analysis*
chemical_list: D003505:Cyclodextrins; D012996:Solutions; D003300:Copper; D002216:Captopril; D010100:Oxygen