Kinetic investigation of Famotidine S-oxidation reaction using potassium caroate. Development and validation of the titrimetric method for the quantitative determination of Famotidine in pure substance and medical preparation
Abstract
Aims: The kinetic studies of Famotidine (FMT) pure substance and medicinal preparation have been carried out in buffer solutions under second-order conditions at the temperature 293 K for the first time. New titrimetric procedures are described for the FMT determination. Materials and Methods: FMT pure substance and tablets have been used in analytical reaction with of KHSO5. The kinetic behavior has been studied by the iodometric method in different pH medium. Results: FMT oxidation reaction has been studied for the S-oxide product under pH=2.0-5.0 and Sulfone product under pH=7.0-8.4. The reaction studied corresponds to the total second order. The Sulfone formation from FMT S-oxide reaction rate constant is in the interval from 14.49 to 32 min-1 L mol-1. FMT has been treated with a measured excess of standard potassium caroate in buffer solution with pH 7, after a contact time of 20 min, the residual oxidant back has been determined by the iodometric titration method. The titrimetric method is applicable over 1-10 mg mL-1 concentration range and the reaction follows 1:2 (FMT:KHSO5) stoichiometry. The method has been validated for precision, accuracy, linearity, robustness and LOQ. The recovery percent ranged from 99.2 to 100.5%, RSD from 1.09 to 1.70 %, LOQ = 0.03 mg mL-1 for pure substance. RSD for tablet formulations has been in the limits from 1.17-2.87 %. Conclusions: The conditions of FMT S-oxide and Sulfone formation have been optimized. The developed procedures are rapid, simple and inexpensive and could be applied to pharmaceutical preparation.
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