STUDY ON THE INTERACTION OF AMITRIPTYLINE HYDROCHLORIDE AND MALONIC ACID BY SPECTROPHOTOMETRIC AND SPECTROFLUORIMETRIC METHODS IN TABLETS: APPLICATION TO CONTENT UNIFORMITY TESTING

摘要

Objective: The objective of this research to study the interaction between amitriptyline hydrochloride in drug products via reaction with mixed acids anhydrides: Application to Content Uniformity Testing . Methods: Malonic acid anhydride (MAA), is a labeling reagent known to react with tertiary amines and forming stable condensation colored product which can be measured either spectrophotometrically, or spectrofluorometrically. Different experimental parameters were established by varying each in turn while keeping others constant. These factors include; effect of concentration of MAA, effect of diluting solvent, effect of heating temperature and time. Results: Linearity of the proposed methods was found to be between 0.5–10 μg/ml μg/ml with good correlation coefficient (0.9998) for spectrophotometrically method, and 0.05–6 μg/ml with good correlation coefficient (0.9998) for spectrofluorometrically method. LOD was found to be 0.168 μg/ml and 0.016 μg/ml, and LOQ was calculated to be 0.510 μg/ml and 0.050 μg/ml for two methods respectively. The % recovery of the proposed methods was found to be 100.06 %-100.07 %. The method was found to be precise as the values of % RSD obtained for both intraday and interday, precision studies were found to be<2.0 %. The molar absorptivity, Sandell sensitivity and Quantum yield were calculated. Also the activation energy, enthalpy, entropy, and Gibbs free energy change of the reaction were evaluated. The methods were applied to the analysis of commercial tablet Tryptizol (10 mg, 25 mg). The study was extended to content uniformity testing. Conclusion: The present study described the successful evaluation of MAA reagent in the development of simple and rapid spectrophotometric and spectroflourimetric methods for the accurate determination of APT in drug substance and drug products. Keywords: Amitriptyline HCl, Malonic acid, Spectrophotometric, Spectrofluorimetric, Activation energy, Quantum yield, Content uniformity.