Nd. Weng et al., INVESTIGATION OF KETO-ENOL-TAUTOMERISM AND IONIZATION OF DOXYCYCLINE IN AQUEOUS-SOLUTIONS, International journal of pharmaceutics, 96(1-3), 1993, pp. 13-21
The keto and enol tautomers of doxycycline were separated by liquid ch
romatography on poly(styrene-divinylbenzene). The keto-enol tautomeris
m occurred between C-11a and C-12. The chemical structure of the tauto
mers was elucidated by on-line and off-line UV spectrophotometry and b
y C-13-NMR spectrometry. The kinetics of the equilibrium were investig
ated in the pH range 1-12. The equilibrium was subject to base catalys
is. The tautomerism was enhanced by protonation of doxycycline. The as
signment of the groups responsible for the micro-ionization of doxycyc
line was discussed. Activation parameters were determined at pH 4.0.