枸橼酸维静宁中杂质Ⅰ的研究

INVESTIGATION OF AN IMPURITY CONTAINED IN PENTOXYVERINE CITRATE

本文通过对枸橼酸维静宁(C_(20)H_(31)O_3N·C_6H_8O_7)的TLC分析,找出了影响枸橼酸维静宁的主要杂质Ⅰ,经TLC纯化制备了杂质Ⅰ的纯品,根据其UV、IR、~1HNMR、MS谱图,确定了杂质Ⅰ的结构(C_(18)H_(27)O_2N·C_6H_8O_7)。根据枸橼酸维静宁的生产工艺,研究了杂质Ⅰ的形成过程,并自行合成了该杂质。合成杂质Ⅰ的UV、IR谱图,TLC、GC行为与枸橼酸维静宁样品中杂质Ⅰ相符;通过一系列实验证明,该杂质是枸橼酸维静宁熔点偏低,出现异嗅味的直接因素;本文还根据生产工艺,探讨了控制杂质Ⅰ产生的方法,以改进后的生产工艺所制枸橼酸维静宁产品的熔点、嗅味都得到明显改善,使产品达到优级品规格。

Pentoxyverine Citrate with antitussive activity presents some urgent problems due to melting point depressing, having unordinary odour and higher reproducing rate. The molecular formula of Pentoxyverine Citrate is C_(20)H_(31)O_3N·C_6H_8O-7 A TLC(AcOEt-CH_3OH-NH_4OH 9: 1: 0.5) method is used to analyze the drug. The main impurity (Ⅰ) affecting the drug purity is searched. The pure(Ⅰ) is obtained by preparative TLC. The structure of (Ⅰ) (C_(18)H_(27)O_2N·C_6H_8O_7) is deduced, from the UV, IR, ~1HNMR and MS spectra.On the basis of the manufacture technology of Pentoxyverine Citrate, the formation of (Ⅰ) is investigated, and then some (Ⅰ) is synthesized. The UV, IR spectra and TLC, GC behavior of the synthetic (Ⅰ) is identical to that of(Ⅰ) contained in the sample of Pentoxyverine Citrate. By the serial experiments, (Ⅰ) does depress the melting point of Pentoxyverine Citrate, and causes the unordinary odour. In accordance with the manufacture technology, the method for controlling the formation of (Ⅰ) is preliminarily studied. The melting point and odour of the Pentoxyverine Citrate produced by improved synthetic method is obviously improved.