碳青霉烯类抗生素的高效液相色谱峰形研究Ⅱ.亚胺培南色谱峰的展宽和裂分

Study of peak profile of carbapenem antibiotics in HPLC Ⅱ. Peak broadening and splitting of impenem

由于亚胺培南在水溶液中以一对构象异构体 (约 2∶ 1)的形式存在 ,因此在某些色谱系统中 ,因构象异构体在色谱过程中相互间转化的速率较低 ,导致亚胺培南峰展宽甚至裂分并与有关物质的分离较差。本文定性地研究了柱温、p H、硅胶、固定相和对离子等对亚胺培南峰形和构象异构体分离的影响。结果显示 ,提高柱温或 p H,选用硅胶柱或 amide C1 6 柱 ,均可改善亚胺培南峰形 ;反之 ,降低柱温或 p H,选用 C8柱或 C1 8柱 ,流动相中添加对离子 ,均有利于构象异构体的分离。在此研究基础上初步提出了适用于注射用亚胺培南 /西司他丁含量测定的 HPL C系统。

Imipenem exists as a mixture of two conformers (approximately 2∶1) in water. Due to the slow kinetics of the conformation change, the HPLC of imipenem may yield peak broadening or splitting and the poor resolution of related substances. In this study, the effects of the column temperature, pH, silica gel, stationary phase and pairing ion on the peak profile and the separation of the imipenem conformers were investigated qualitatively. It showed that the improvement of peak profile was favored by an increase of column temperature or pH, using silica gel column or Amide C 16 column. Conversely, the separation selectivity of conformers could be improved with decreasing column temperature or pH, using C 8 column or C 18 column and adding pairing ion in the mobile phase. An HPLC system suitable to the determination of imipenem/cilastatin for injection was established.