Characterization of Non-Protein Colloidal Plasma Volume Expanders

在截至2000年9月30日的报告年度内，CBER没有对该项目进行任何工作。然而，作为Hetastarch原料药生产新方法验证的一部分，奥地利费森尤斯卡比公司（FKA）对CBER提供的6批Hetastarch和4批创新Hetastarch测定了各种重量平均值和数平均分子量（分别为Mw和Mn）值。FKA采用复杂的SE-HPLC方法，需要独特的标准进行校准。尽管如此，所得数据现在提供了一种评估商业多角度激光光散射- se - hplc （MALLS-SE-HPLC）方法的能力的方法，该方法可以准确地确定分数GTE 50,000 Mn的Hetastarch值，该值可能与效价（即体内肿瘤潜能）更相关，而不是整体Mn（或整体Mw），因为分子量lte 50,000的分子会迅速从血管中清除。我们注意到，Wyatt的MALLS-SE-HPLC方法可以相对准确地测定整体的Mw值（目前用于监管目的），但由于SE-HPLC分布中较低分子量物种的散射效率相对较低，因此不能准确测定整体的Mn值。

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.