Abstract

KINETICS OF OXIDATION OF PHARMACEUTICAL DRUG DOXYCYCLINE HYDROCHLORIDE BY CHLORAMINE-T IN NaOH MEDIUM. A MECHANISTIC STUDY

Poorigali Rangaswamy Rangaraju, Thimmappa Venkatarangaiah Venkatesha* andRangegowda Ramachandrappa

Abstract

The kinetics of oxidation of doxycycline hydrochloride(DOX) by chloramine-T (CAT) has been investigated in NaOH medium at 303 K. The Stoichiometry of the reaction was found to be 1:1 and the oxidation product of DOX, 1,4,4a,5,5a,6,11,12a-octahydro- 3,5,10,12,12a-pentahydroxy-6-methyl-1,4,11-trioxotetracene-2- carboxamide is identified by the spot tests and further by LC-MS spectral analysis. The reaction followed first-order kinetics with respect to [CAT]0 , [DOX]0 and fractional-order with [OH-]0 . The effect of added halide ions, reduction product, p-toluene sulfonamide (PTS), ionic strength (NaClO4) and dielectric constant of the medium was studied on the rate of reaction. A mechanism was proposed on the basis of experimental results. The activation parameters with respect to the slow step of the mechanism were evaluated, and the thermodynamic parameters was also determined and discussed.

Keywords: Kinetics, Doxycycline hydrochloride, oxidation, chloramine-T, mechanism.