International journal of pharmaceutics vol:96 issue:1-3 pages:13-21
The keto and enol tautomers of doxycycline were separated by liquid chromatography on poly(styrene-divinylbenzene). The keto-enol tautomerism occurred between C-11a and C-12. The chemical structure of the tautomers was elucidated by on-line and off-line UV spectrophotometry and by C-13-NMR spectrometry. The kinetics of the equilibrium were investigated in the pH range 1-12. The equilibrium was subject to base catalysis. The tautomerism was enhanced by protonation of doxycycline. The assignment of the groups responsible for the micro-ionization of doxycycline was discussed. Activation parameters were determined at pH 4.0.