Some Observations on the Kinetics of the C∙4 Epimerization of Tetracycline

• Published in: Journal of pharmaceutical sciences 1963-08, Vol.52 (8), p.752-756
• Main Authors: Remmers, Edward G., Sieger, George M., Doerschuk, Albert P.
• Format: Article
• Language: English
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600520809

The C∙4 epimerization of tetracycline has been shown to follow the kinetics of a first-order reversible reaction. Phosphate and citrate ions increased the rate of C∙4 epimerization. The reaction rate in either 1.00 molar phosphate or 1.00 molar citrate buffer at pH4.0 and 23° was approximately 70 times the rate observed in distilled water under the same conditions of temperature and pH. An Arrhenius plot indicated that the apparent energy of activation for the C∙4 epimerization of tetracycline at pH4.0 and 0.10 molar phosphate buffer was approximately 20 kilo-calories/gram-mole. The equilibrium concentration and the rate at which equilibrium was approached were dependent on the pH. Of the five pH levels studied, a maximum C∙4 epimer level of 55 per cent at equilibrium occurred at pH3.2. Of the five pH levels studied, the rate at which equilibrium was approached was highest at pH3.2, 4.0, and 5.0.