The kinetics of the deiodination of levothyroxine in aqueous solution were studied over the pH range 1 to 12. Temperature dependence of the reaction was also studied. The log k - pH profile indicated that the kinetics of deiodination include proton attack on the anion and dianion in acidic solution and water attack on the anion and dianion in alkaline solution. A possible mechanism of the deiodination was discussed. The solid-state stability of levothyroxine sodium was studied at elevated temperatures; and the compound was found to undergo deamination on heating. The decomposition follows biphasic first-order kinetics, with the most rapid decomposition occurring at the beginning of heating.
In aqueous solutions, dalvastatin (1) undergoes epimerization as well as hydrolysis. The transformation of the drug was studied as a function of pH at 25 degrees C in aqueous solutions containing 20% acetonitrile. At all pH values, first-order plots for the conversion are biphasic, indicating rapid equilibration of 1 with its epimer (2) and slower hydrolysis of 1 to the corresponding beta-hydroxy acid (3). Apparent first-order rate constants for the biexponential equation are given as a function of pH. The alkyl-oxygen cleavage of the lactone ring results in the epimerization of 1 to 2, whereas the acyl-oxygen cleavage results in the hydrolysis of 1 to 3. The epimerization is an SN1 reaction reaching an equilibrium of [1]eq/[2]eq = 1.27. The epimerization rate is increased with an increase in the water content of the solvent. The hydrolysis of 1 to 3 is acid and base catalyzed. The hydrolysis is reversible in acidic media and irreversible in neutral and basic media. At pH values greater than 9, the hydrolysis reaction proceeds more rapidly than the epimerization.
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