Kinetics of the acidic and enzymatic hydrolysis of benazepril HCl studied by LC.
A reversed-phase high-performance liquid chromatographic (HPLC) method was developed and validated for the kinetic investigation of the chemical and enzymatic hydrolysis of benazepril hydrochloride. Kinetic studies on the acidic hydrolysis of benazepril hydrochloride were carried out in 0.1 M hydrochloric acid solution at 50, 53, 58 and 63 degrees C. Benazepril hydrochloride appeared stable in a pH 7.4 phosphate buffered solution at 37 degrees C and showed susceptibility to undergoing in vitro enzymatic hydrolysis with porcine liver esterase (PLE) in a pH 7.4 buffered solution at 37 degrees C. Benazeprilat appeared to be the major degradation product in both (chemical and enzymatic) studies of hydrolysis. Statistical evaluation of the proposed HPLC methods revealed their good linearity and reproducibility. Relative standard deviation (R.S.D.) was less than 4.76, while detection limits for benazepril hydrochloride and benazeprilat were 13.0 x 10(-7) and 9.0 x 10(-7) M, respectively. Treatment of the kinetic data of the acidic hydrolysis was carried out by non-linear regression analysis and k values were determined. The kinetic parameters of the enzymatic hydrolysis were determined by non-linear regression analysis of the data using the equation of Michaelis-Menten.
Gana
M
M
Department of Pharmacy, Division of Pharmaceutical Chemistry, University of Athens, Panepistimiopolis Zografou, GR-157 71, Athens, Greece.
Panderi
I
I
Parissi-Poulou
M
M
Tsantili-Kakoulidou
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D001552:Benzazepines / Q000032:analysis / Q000737:chemistry*; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D015394:Molecular Structure; D011355:Prodrugs / Q000737:chemistry*; D015203:Reproducibility of Results
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D011355:Prodrugs; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; C052133:benazeprilat; C044946:benazepril