Characterization of Colloidal Plasma Volume Expanders

摘要：在截至2001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，在2000年，作为验证一种新的红花蛇舌草药材制造方法的一部分，奥地利Fresenius Kabi(FKA)测定了由CBER提供的6批红花蛇舌草和4个创新者红花蛇舌草样品的不同重量平均和数均相对分子质量(分别为Mw和Mn)值。FKA使用一种非商业的、复杂的SE-HPLC方法，该方法需要一个独特的标准进行校准，并已得到CBER的验证。然而，所得到的数据现在提供了一种评估商业MALLS的能力的方法-怀亚特技术公司的SE-HPLC方法来准确地确定组分GTE 50,000的锰的异构体的值，由于分子量LT 50,000的分子被迅速从血管系统中清除，所以该值可能更与效力(即在体内的肿瘤势)有关而不是与整体的锰(或整体的MW)有关。我们注意到，Wyatt Technology的Malls-SE-HPLC方法允许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，因此无法准确测定整体的Mw。如果2002财年时间允许，我们将要求怀亚特科技公司通过MALLS-SE-HPLC测定上述4个CBER样品中GTE 50,000的整体和部分GTE 50,000的Mw和Mn值，以及上面报告的6批FKA Hetastore的Mw和Mn值，如果我们能够获得这些FKA材料的样品。

Summary: During the reporting year ending September 30, 2001, no work was performed on this project at CBER. However, during the year 2000, as part of the validation of a new method of manufacturing Hetastarch drug substance, Fresenius Kabi Austria (FKA) determined various weight average and number average molecular weight (Mw and Mn, respectively) values for 6 lots of their Hetastarch and 4 samples of innovator Hetastarch, supplied by CBER. FKA utilizes a non-commercial, complicated SE-HPLC method that requires a unique standard for calibration and that has been validated by CBER. Nevertheless, the resultant data now provide a way of assessing the ability of the commercial 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 the MALLS-SE-HPLC methodology of Wyatt Technology 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. If time permits during FY 2002, we will request that Wyatt Technology Corp. determine by MALLS-SE-HPLC the Mw and Mn values of the Whole and Mn of the Fraction GTE 50,000 of the 4 CBER samples referenced above in addition to the 6 lots of FKA Hetastarch for which values are reported above if we can procure samples of these FKA materials.