Kinetic study on the acidic hydrolysis of lorazepam by a zero-crossing first-order derivative UV-spectrophotometric technique

A zero-crossing first-order derivative UV-spectrophotometric technique for monitoring the main degradation product, 6-chloro-4-(2-chlorophenyl)-2-quin azoline carboxaldehyde, was developed to study the acidic hydrolysis of lor azepam in hydrochloric acid solutions of 0.1 M. Due to the complete overlap of the spectral bands of the parent drug and the hydrolysis product (the r ange between their spectral maxima was only 3 nm), the graphical methods of derivative spectrophotometry were not efficient. The relative standard dev iation of the proposed technique was less than 2.4% and the detection limit was 6.6 x 10(-8) M. Accelerated studies at higher temperatures have been e mployed that enable rapid prediction of the long-term stability of this dru g. Pseudo-first order reaction kinetics was observed. Kinetic parameters, k (obs) and t(1/2), were calculated, which were similar to those estimated by an HPLC method developed in our laboratory. (C) 1999 Elsevier Science B.V. All rights reserved.