Kinetics of degradation of levothyroxine in aqueous solution and in solid state.
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.
Won
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Analytical and Physical Chemistry Department, Rhône-Poulenc Rorer Central Research, Fort Washington, Pennsylvania 19034.
D002851:Chromatography, High Pressure Liquid; D004304:Dosage Forms; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007455:Iodine / Q000378:metabolism; D015394:Molecular Structure; D012995:Solubility; D012996:Solutions; D013974:Thyroxine / Q000493:pharmacokinetics*; D014867:Water
D004304:Dosage Forms; D012996:Solutions; D014867:Water; D007455:Iodine; D013974:Thyroxine