Isoxazoles. 9. Degradation kinetics of 4-(isoxazolylamino)-1,2-naphthoquinone in acidic aqueous solution

J Pharm Sci. 1994 Oct;83(10):1457-60. doi: 10.1002/jps.2600831018.

Abstract

The degradation kinetics of N-(5-methyl-4-isoxazolyl)-4-amino-1,2-naphthoquinone (1) was studied in aqueous solution over a pH range of 0.65-7.50, at 35 degrees C and at a constant ionic strength of 0.5. The degradation rates were determined by high-pressure liquid chromatography and were observed to follow pseudo-first-order kinetics with respect to the concentration of 1. The pH-rate profile was linear with slope -1 under acidic pH, becoming pH independent from 3.50 to 7.50. Good agreement between the theoretical pH-rate profile and the experimental data supports the proposed degradation process. The catalytic rate constants for hydrogen ion and water were kH = 0.901 M-1 h-1 and k0 = 1.34 x 10(-3)h-1, respectively. These data are appropriate to develop a stable dosage form of 1. The accuracy, peak sharpness, and asymmetry factor for the analytical method were determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • Drug Stability
  • Hydrogen-Ion Concentration
  • Isoxazoles / chemistry*
  • Kinetics
  • Naphthoquinones / chemistry*
  • Reference Standards
  • Reproducibility of Results
  • Solutions
  • Sulfadiazine / chemistry
  • Temperature
  • Water / chemistry*

Substances

  • Isoxazoles
  • N-(5-methyl-4-isoxazolyl)-4-amino-1,2-naphthoquinone
  • Naphthoquinones
  • Solutions
  • Water
  • Sulfadiazine