Kinetics of concomitant degradation of tetracycline to epitetracycline, anhydrotetracycline, and epianhydrotetracycline in acid phosphate solution.

The concentrations of tetracycline, epitetracycline, anhydrotetracycline, and epianhydrotetracycline in pH 1.5 phosphate solution were followed as a function of time at four temperatures. Separation and quantification of all four species were accomplished using high-pressure liquid chromatography. Through nonlinear regression analysis, rate constants for the reversible first-order epimerization of tetracycline and anhydrotetracycline and for the first-order dehydration of tetracycline and epitetracycline were obtained. Solutions to the differential equations obtained through Laplace transforms successfully predict concentrations found experimentally. The energy of activation for each reaction step was calculated and ranged from 15 to 27 kcal/mole. The rate constants for tetracycline and epitetracycline dehydration conform with those of earlier studies that used different experimental methods. The study shows that epimerization of tetracycline and anhydrotetracycline can take place at a low pH.