The control of high molecular weight
impurities in β-lactam
antibiotics hasbeen paid a great attention by pharmaceutical
manufacturer, clinical medicine and drugadministrator in the world. A novel gel filtration chromatography on Sephadex G-10 toseparate the high molecular weight
impurities has been developed recently<5>. But accuratequantitation is still a remaining problem to be resolved. Although external standard methodor normalization method theoretically could be used, it is difficult to perform in the polymerquantity due to its heterogeneity and the small content. Based on some second interactionsamong β-lactam themselves which bind the
antibiotics together forming a non-covalentpolymers in a special condition,which caused the antibiotics like the high molecular weightimpurities showing only one peak with Kav = 0 in Sephadex G-10 gel chromatographicsystem, a novel quantitative method, termed external standard method of reference oncsclf(ESMOROS), for determination of the high molecular weight impurities is developed inSephadex G-10 gel filtration chromatographic system. The ESMOROS method thatcombines the advantages of an external method and of a normalization method, does not needsome special reference standards, but can accurately quantitate thc impurities. Some effectsinfluencing the accuracy of the ESMOROS are also discussed.