β-内酰胺抗生素在Sephadex G—10凝胶色谱中色谱行为的定量关系  

Quantitative Chromatographic Behavior and the Structure Relationship of β Lactam Antibiotics on Sephadex G-10 Gel Chromatography

作　　者：胡昌勤[1,2] 孙丽丽[1,2] 金少鸿[1,2] 

机构地区：[1]中国药品生物制品检定所 [2]北京医科大学药学院

出　　处：《药物分析杂志》1997年第2期78-84,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：用β－内酰胺抗生素的一阶价分子连接性指数（１Ｘｖ）、一阶分子连接性指数（１Ｘ）、分子的环状结构数（ｆ）及分子的非氢原子原子总数（Ｎ）等参数描述β－内酰胺抗生素的结构特征，利用回归分析的方法发现，β－内酰胺抗生素的ｋ值与其１Ｘｖ／ｆ的对数值呈明显相关；进一步分析，将β－内酰胺抗生素按其结构分为３类：Ⅰ类包括所有青霉素，Ⅱ类包括３位和７位侧链均不含较大环结构或仅有１个侧链含较大环结构的头孢菌素，Ⅲ类包括３位和７位侧链均有较大环平面结构的头孢菌素，发现Ⅰ类青霉素类抗生素的ｋ值和其诸结构参数间的关系较好地符合关系式：ｋ＝ａ＋ｂｌｎ（１Ｘｖ／ｆ）＋ｃ１Ｘｖ＋ｄ１Ｘ＋ｅ（１Ｘ－１Ｘｖ）／Ｎ（１）Ⅱ类和Ⅲ类头孢菌素类抗生素的ｋ值与其诸结构参数间的关系更符合关系式：ｋ＝ａ＋ｂ１Ｘｖ＋ｃ１Ｘ＋ｄ１Ｘ２ｖ＋ｅ１Ｘ２＋ｆ１Ｘｖ１Ｘ（２）并发现流动相中不同阴离子的１Ｘｖ和其平均电荷数（Ｑ）之和（１Ｘｖ＋Ｑ）与溶质的ｋ值呈线性关系；溶质的半峰宽（Ｗ１／２）和其保留时间（ｔＲ）呈线性关系；ｋ值的对数和流动相缓冲液浓度（Ｃ）的对数呈线性关系。Control of high molecular weight impurities in β lactam antibiotics plays an important role in reducing anaphylaxis caused by the antibiotics in clinical therapy.Usually,gel chromatography is a routine method selected for the quality control,and the Sephadex G-10 chromatographic system is a convenient one. By choosing some structure parameters,i.e.first order valence molecular connectivity index( 1X v),first order molecular connectivity index( 1X),ring number of the molecule(f) and the number of total atoms of the molecule except hydrogen atoms(N),using regression method,it was found that there was a close relationship between k of β lactam antibiotics and the ln 1X v/f values.Further studies indicated that all β lactam antibiotics could be divided into three classes:class one included all penicillins with a close relationship as equation(1) k=a+bln( 1X v/f)+c 1X v+d 1X+e( 1X- 1X v)/N (1) class two,in which there was no ring structure or only one ring structure in 3 or 7side chain and class three,in which there were two or more than two ring structures in the side chains were cephalosporins and fited another equation as follows, k=a+b 1X v+c 1X+d 1X 2 v+e 1X 2+f 1X v 1X (2) It was found also that a close linear relationship between k existed of β lactam antibiotics and the 1 X v+Q value of mobile phase(Q is the mean of electronic charges of negative ions in the mobile phase),W 1/2 of the chromatographic peak and its retention time(t R)had a close linear relationship,ln k and lnC(concentration of buffer as mobile phase)had a close linear relationship too.Those results could be used as a basis for quickly optimizing the chromatographic condition of β lactam antibiotics on Sephadex G-10 gel chromatographic system.

关 键 词：Β内酰胺 抗生素 凝胶色谱 葡聚糖凝胶 定量结构 

分 类 号：R978.11[医药卫生—药品] R914.1[医药卫生—药学]