KINETIC-STUDY ON THE DEGRADATION OF PRAZEPAM IN ACIDIC AQUEOUS-SOLUTIONS BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND 4TH-ORDER DERIVATIVEULTRAVIOLET SPECTROPHOTOMETRY
Ha. Archontaki et al., KINETIC-STUDY ON THE DEGRADATION OF PRAZEPAM IN ACIDIC AQUEOUS-SOLUTIONS BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND 4TH-ORDER DERIVATIVEULTRAVIOLET SPECTROPHOTOMETRY, Journal of pharmaceutical and biomedical analysis, 17(4-5), 1998, pp. 739-750
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.