THE KINETICS AND MECHANISM OF THE HYDROLYSIS OF CYCLOPENTOLATE HYDROCHLORIDE IN ALKALINE-SOLUTIONS

Cyclopentolate hydrochloride (Cy . HCl) is an ester of a substituted benzeneacetic acid, having N,N-dimethylaminoethanol as the alcohol moiety. A reversed-phase HPLC assay was employed to investigate the kinetics of degradation of Cy . HCl. The influence of pH, buffers, and temperature was studied in alkaline solutions. The degradation follows (pseudo) first-order kinetics at 50 degrees C. Results indicate that it degrades very rapidly at higher pH values. Phenylacetic acid and alpha-(1-hydroxycyclopentyl)benzeneacetic acid were isolated and identified as the degradation products. The reaction mechanism appears to follow a parallel scheme where phenylacetic acid and alpha-(1-hydroxycyclopentyl)benzeneacetic acid are formed simultaneously. It is proposed that alpha-(1-hydroxycyclopentyl)benzeneacetic acid is formed by normal ester hydrolysis. Phenylacetic acid is formed via a six-membered transition state and its formation requires the assistance of the hydroxyl group from the adjacent cyclopentanol moiety.