Development of a kinetic reaction rate limited study on degradation of impurity profile for the estimation of acetaminophen in acidic aqueous solution for pharmaceutical dosage form by High Performances Liquid Chromatography (HPLC).

Author(s): Dilip Kumar Bevara*, Nageswara Rao Anipindi

Abstract

A reaction-limited model for impurity profile is developed for the acetaminophen which consists of degradation impurity as 4- Amino phenol including ten other potential impurities. As many ways of the synthetic routes for acetaminophen it has been identified the impurities are of eleven. Out of which many degrading impurities, 4-Amino phenol is one of the major degradant. And remaining Organic Impurities that may appear in acetaminophen preparations are process-related impurities. Impurity evolution process is considered from Reverse-phase liquid chromatography (RPLC) which is the method of choice for the analysis of basic compounds. The chromatographic behavior of acidic and basic substances is closely related to their structure and is easily influenced by many factors, Such as pH, molarity and Composition of the Mobile Phase. Determination of kinetic reaction for acetaminophen and its main degradation of impurity as 4- aminophenol was developed and method have been validated for the same through the High Performances Liquid Chromatography for all potential eleven impurities. Chromatographic separation has been obtained on an Intersil ODS 3V using gradient elution of having mobile phase A&B. In Mobile phase-A of 0.01M Di-potassium hydrogen phosphate adjusted pH 7.0 diluted with ortho-phosphoric acid and Mobile phase- B is the mixture of 800ml methanol and 200ml of 0.01M Di-potassium hydrogen phosphate adjusted pH 7.0 diluted with ortho-phosphoric acid. Analysis time did not exceed 75minutes and good resolution peak shapes and asymmetric have retained. The method has been successfully obtained for the study of kinetic degradation of acetaminophen with respect to its degradation impurity of the 4-aminophenoland other process related impurities. A kinetic investigation of acidic hydrolysis of acetaminophen was carried out in hydrochloride solutions of 0.3N, 0.5N and 1.0N by monitoring the parent compound itself with respect to its main degradant. The order of acetaminophen followed pseudo-first order kinetics. The activation energy could be extended from the Arrhenius plot and it was found to be 21.2Kcal/mol.

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