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，作为一种制造杂交酯药材新方法的验证的一部分，奥地利Fresenius Kabi(FKA)已经测定了由CBER提供的6批杂交酯和4批次创新剂杂交酯的各种重量平均和数均相对分子质量(分别为Mw和Mn)值。FKA使用了一种复杂的SE-HPLC方法，需要一个独特的标准进行校准。然而，现在所得到的数据提供了一种评估商业多角度激光光散射-SE-HPLC法(MALLS-SE-HPLC法)的能力的方法，该方法能够准确地确定组分GTE 50,000中的锰的异构体的值，该值可能更与效力(即在体内的肿瘤势)有关，而不是与整体(或整体的MW)的锰有关，因为分子量LT 50,000的分子可以迅速从血管系统中清除。我们注意到，怀亚特的MALLS-SE-HPLC法允许确定相对准确的整体MW值(目前用于监管目的)，但由于SE-HPLC分布中较低分子量物种的散射效率相对较低，因此无法准确确定整体的MW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.