Determination of atenolol, chlorthalidone and their degradation products by TLC-densitometric and chemometric methods with application of model updating

Abstract

In this work two well known antihypertensive drugs that are administered in combination and provide greater therapeutic effects than with either drug alone are selectively determined in the presence of their degradation products. Two chemometric methods and TLC-Densitometric one have been developed for the selective determination of Atenolol (ATE) and Chlorthalidone (CLT) along with their hydrolytic degradation products. The developed chemometric models are principal component regression (PCR) and partial least squares (PLS). These models have been updated to be used for prediction of ATE and CLT in another dosage form in which Amiloride HCl (AMH) is included. The updated models are capable of predicting the concentrations of the three components of the new dosage form with good accuracy and precision without reconstruction of the calibration set. The developed TLC-Densitometric method depends upon quantitative densitometric separation of thin layer chromatogram of ATE, CLT, Atenolol degradation product (ATE Deg) and Chlorthalidone degradation product (CLT Deg) using silica gel plates at 227 nm and chloroform: methanol: ethyl acetate: ammonia solution (75: 28: 2: 1.6, by volume) as a developing system. The suggested methods have been used for the determination of the studied drugs in their pharmaceutical formulations and the results were statistically compared to the reported RP-HPLC method.