Characterization of Non-Protein Colloidal Plasma Volume Expanders

在截至2000年9月30日的报告年度内，CBER没有就该项目开展任何工作。 然而，作为羟乙基淀粉原料药新生产方法验证的一部分，Fresenius Kabi Austria（FKA）测定了CBER提供的6批羟乙基淀粉和4批创新羟乙基淀粉的各种重均和数均分子量（分别为Mw和Mn）值。 FKA采用复杂的SE-HPLC方法，需要唯一的标准品进行校准。 尽管如此，所得数据现在提供了一种评估商业多角度激光散射-SE-HPLC的能力的方法Wyatt Technology，Corp.的MALLS-SE-HPLC方法，以准确测定级分GTE 50，000的Mn的羟乙基淀粉值，一个可能更与效力相关的值由于分子量LT 50，000的分子从脉管系统中快速清除，因此整体的Mn（或整体的Mw）比整体的Mn（即，体内粘附潜力）高。 我们注意到，Wyatt的MALLS-SE-HPLC方法允许测定相对准确的整体Mw值（目前用于监管目的），但由于SE-HPLC分布中较低分子量物质的散射效率相对较低，因此不允许准确测定整体Mn。

During the reporting year ending September 30, 2000, no work was performed on this project at CBER. However, as part of the validation of a new method of manufacturing Hetastarch drug substance, Fresenius Kabi Austria (FKA) has determined various weight average and number average molecular weight (Mw and Mn, respectively) values for 6 lots of their Hetastarch and 4 lots of innovator Hetastarch, supplied by CBER. FKA utilizes a complicated SE-HPLC method that requires a unique standard for calibration. Nevertheless, the resultant data now provide a way of assessing the ability of the commercial multi-angle laser light scattering-SE-HPLC (MALLS-SE-HPLC) method of Wyatt Technology, Corp. to accurately determine values for Hetastarch of Mn of the Fraction GTE 50,000, a value probably more related to potency (i.e. in vivo oncotic potential) than Mn of the Whole (or Mw of the Whole) since molecules of molecular weight LT 50,000 are rapidly cleared from the vasculature. We note that Wyatt's MALLS-SE-HPLC methodology allows the determination of relatively accurate values of Mw of the Whole (currently used for regulatory purposes) but does not permit accurate determination of Mn of the Whole due to the relatively low scattering efficiency of the lower molecular weight species in the SE-HPLC distribution.