Archontaki H A, Panderi I E, Gikas E E, Parissi-Poulou M
Department of Chemistry, University of Athens, Panepistimiopolis, Greece.
J Pharm Biomed Anal. 1998 Aug;17(4-5):739-50. doi: 10.1016/s0731-7085(97)00246-x.
A reversed-phase HPLC method was developed for the kinetic investigation of the acidic hydrolysis of prazepam which was carried out in hydrochloric acid solutions of 0.01, 0.1 and 1.0 M. In addition, a fourth-order derivative method for monitoring the parent compound itself was proposed and evaluated. One intermediate was observed by HPLC, which should be formed from breakage of the azomethine linkage. Further slow hydrolysis of the amide bond led to the benzophenone product that was isolated and identified. The mechanism of hydrolysis was biphasic, showing a consecutive reaction with a reversible step. Relative standard deviation 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 and 6.7 x 10(-7)M for the latter. Accelerated studies at higher temperatures were employed. Results of HPLC and fourth-order derivative methods were statistically the same.
建立了一种反相高效液相色谱法，用于在0.01、0.1和1.0 M盐酸溶液中对普拉西泮的酸性水解进行动力学研究。此外，还提出并评估了一种用于监测母体化合物本身的四阶导数法。通过高效液相色谱法观察到一种中间体，它应该是由亚甲胺键断裂形成的。酰胺键的进一步缓慢水解导致分离并鉴定出二苯甲酮产物。水解机制是双相的，显示出一个具有可逆步骤的连续反应。高效液相色谱法的相对标准偏差小于2%，导数法的相对标准偏差小于5%。前一种方法的检测限为1.2×10(-7) M，后一种方法的检测限为6.7×10(-7) M。采用了在较高温度下的加速研究。高效液相色谱法和四阶导数法的结果在统计学上是相同的。
