Panderi I, Archontaki H, Gikas E, Parissi-Poulou M
Department of Pharmacy, University of Athens, Panepistimiopolis, Greece.
J Pharm Biomed Anal. 1998 Jun;17(2):327-35. doi: 10.1016/s0731-7085(97)00201-x.
A kinetic study on the acidic hydrolysis of bromazepam was carried out in 0.01 M hydrochloric acid solution at 25 and 95 degrees C. A reversed-phase HPLC method was developed and validated for the determination of bromazepam and its degradation products. Bromazepam degraded by a consecutive reaction with a reversible first step. Two degradation products were isolated and identified by infrared, 1H and 13C nuclear magnetic resonance and mass spectroscopy. Spectroscopic data indicated that N-(4-bromo-2-(2-pyridylcarbonyl)phenyl)-2-aminoacetamide was the intermediate degradation product of this acid hydrolysis, whereas 2-amino-5-bromophenyl-2-pyridylmethanone was the final one. Therefore, the mechanism of this acid-catalysed hydrolysis involved initial cleavage of the 4,5-azomethine bond, followed by slow breakage of the 1,2-amide bond. Statistical evaluation of the HPLC method revealed its good linearity and reproducibility. Detection limits were 3.8 x 10(-7) M for bromazepam, 6.25 x 10(-7) M for the intermediate and 8.16 x 10(-7) M for the benzophenone derivative.
在25℃和95℃下，于0.01M盐酸溶液中对溴西泮的酸性水解进行了动力学研究。开发并验证了一种反相高效液相色谱法，用于测定溴西泮及其降解产物。溴西泮通过一个第一步可逆的连续反应进行降解。分离出两种降解产物，并通过红外光谱、1H和13C核磁共振以及质谱进行了鉴定。光谱数据表明，N-(4-溴-2-(2-吡啶羰基)phenyl)-2-氨基乙酰胺是该酸水解的中间降解产物，而2-氨基-5-溴苯基-2-吡啶基甲酮是最终产物。因此，这种酸催化水解的机制包括4,5-甲亚胺键的初始断裂，随后是1,2-酰胺键的缓慢断裂。对高效液相色谱法的统计评估显示其具有良好的线性和重现性。溴西泮的检测限为3.8×10(-7)M，中间产物的检测限为6.25×10(-7)M，二苯甲酮衍生物的检测限为8.16×10(-7)M。
