The effect of temperature and pH on the deacetylation of diamorphine in aqueous solution and in human plasma

J Pharm Pharmacol. 1992 Jul;44(7):606-8. doi: 10.1111/j.2042-7158.1992.tb05474.x.

Abstract

The effect of temperature on the kinetics of the deacetylation of diamorphine and 6-monoacetylmorphine was studied in human plasma. Diamorphine was rapidly and quantitatively degraded to 6-monoacetylmorphine with initial half-lives of 354, 18 and 3 min at temperatures of 4, 25 and 37 degrees C, respectively. Further deacetylation to morphine was not detected. In aqueous solution, diamorphine was quantitatively degraded to give 6-monoacetylmorphine as the major product and morphine as a minor product, the rate of deacetylation being dependent on temperature and pH. At pH 4.0 and 5.6 diamorphine had a half-life of greater than 14 days at all temperatures but at alkaline pH diamorphine was rapidly deacetylated. The rate of deacetylation of 6-monoacetylmorphine was consistently slower than that of diamorphine under identical conditions of pH and temperature. A method is described for the rapid stabilization and subsequent assay of diamorphine in plasma which will prevent errors in estimation of the drug due to unwanted hydrolysis.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Heroin / blood
  • Heroin / pharmacokinetics*
  • Humans
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Morphine Derivatives / blood
  • Morphine Derivatives / pharmacokinetics*
  • Temperature

Substances

  • Morphine Derivatives
  • Heroin
  • 6-O-monoacetylmorphine