Development of Stability Indicating Assay Method for TAZQ a Potential Anti cancer Agent and Comparative Stability Analysis of Digoxin and and#946; Acetyldigoxin

Abstract

newline vii newlineABSTRACT newline7,8,9,10-Tetrahydroazepino[2,1b]quinazolin-12(6H)-one (TAZQ), a synthetic vasicine analog, has been reported as bronchodilator, anti-inflammatory, anti-tussive, anti-arthritic, anti-asthmatic and anti-cancer compound. It is presently under pre-clinical studies (CSIR-IIIM, Jammu, India) for anti-cancer activity. The degradation studies and stability indicating assay method have not been reported for TAZQ as yet. So, novel validated RP-HPLC stability indicating assay was developed for the estimation of TAZQ. The method was found to be linear, accurate, precise, robust, suitable, sensitive, specific and stability indicating, as per the regulatory guidelines. Forced degradation studies of TAZQ were carried out and it was found resistant to degradation under stress. The method was established as specific stability indicating assay as it was able to determine TAZQ unequivocally in the stressed samples. The developed method is superior to the earlier reported method in terms of cost, simplicity of operation and rapidity of analysis. The method is suitable for routine quality control and stability analysis of TAZQ. newlineDigoxin and and#946;-acetyldigoxin are the most important cardiac glycosides in the marketplace. and#946;-Acetyldigoxin is a better absorbed prodrug of digoxin. It is ambiguous if and#946;-acetyldigoxin meets fundamental pharmaceutical objective of prodrug design to exhibit better chemical stability than the parent drug. Both digoxin and and#946;-acetyldigoxin are narrow therapeutic index drugs, thus, the concept of stability is even more significant. Novel RP-HPLC methods for respective determination of digoxin and and#946;-acetyldigoxin were developed and validated according to regulatory guidelines. The methods were found to be linear, accurate, precise, robust, suitable, sensitive, specific and stability indicating. Digoxin and and#946;-acetyldigoxin were subjected to accelerated and forced degradation testing. Accelerated testing was carried out at 40±2°C and 75±5% RH. The degradation samples were analyzed using developed analytical methods. The peaks of degradation products were well separated from the respective peak of analyte. It confirmed stability indicating capacity of the developed methods. Degradation kinetics studies reveal that degradation followed apparent zero order kinetics. A comparison, with respect to stability, was drawn between digoxin and and#946;-acetyldigoxin, for each degradation condition. Except for the photo degradation condition, and#946;-acetyldigoxin appeared to be more stable chemically, as compared to digoxin.