KINETIC-STUDY ON THE DEGRADATION OF PRAZEPAM IN ACIDIC AQUEOUS-SOLUTIONS BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND 4TH-ORDER DERIVATIVEULTRAVIOLET SPECTROPHOTOMETRY

A reversed-phase HPLC method was developed for the kinetic investigati on of the acidic hydrolysis of prazepam which was carried out in hydro chloric acid solutions of 0.01, 0.1 and 1.0 M. In addition, a fourth-o rder derivative method for monitoring the parent compound itself was p roposed and evaluated. One intermediate was observed by HPLC, which sh ould be formed from breakage of the azomethine linkage. Further slow h ydrolysis of the amide bond led to the benzophenone product that was i solated and identified. The mechanism of hydrolysis was biphasic, show ing a consecutive reaction with a reversible step. Relative standard d eviation was less than 2% for HPLC and less than 5% for the derivative method. Detection limits were 1.2 x 10(-7) M for the former method an d 6.7 x 10(-7) M for the latter. Accelerated studies at higher tempera tures were employed. Results of HPLC and fourth-order derivative metho ds were statistically the same. (C) 1998 Elsevier Science B.V. All rig hts reserved.