Lee J K, Deluccia F J, Kelly E L, Davidson C, Borger F R
Rorer Central Research, Horsham, PA 19044.
J Chromatogr. 1988 Jul 1;444:141-52. doi: 10.1016/s0021-9673(01)94017-8.
Recent reports have expressed concern about the safety of intravenous human immunoglobulin G (IgG) preparations. Evidence seems to indicate that aggregates in these formulations are responsible for several adverse reactions in some patients, including anaphylaxis and dyspnea. Therefore, monitoring the molecular size distribution of IgG in these products is essential for ensuring their safety. This paper describes a sensitive and precise two-stage high-performance liquid chromatographic method for determining the molecular size distribution profile of IgG in an intravenous formulation stabilized with albumin. In the first step, all molecular forms of IgG are separated from all molecular forms of albumin by anion-exchange chromatography. In the second stage, a portion of the collected IgG fraction is re-chromatographed by size-exclusion chromatography and separated into its aggregate, dimer, and monomer components. Although some minor losses of aggregate do occur in the procedure, the overall molecular size distribution is not significantly affected. The method described is both time-efficient and accurate, and represents an improvement over existing methods.
最近的报告对静脉注射用人免疫球蛋白G（IgG）制剂的安全性表示担忧。证据似乎表明，这些制剂中的聚集体是导致一些患者出现多种不良反应的原因，包括过敏反应和呼吸困难。因此，监测这些产品中IgG的分子大小分布对于确保其安全性至关重要。本文描述了一种灵敏且精确的两步高效液相色谱法，用于测定用白蛋白稳定的静脉制剂中IgG的分子大小分布谱。第一步，通过阴离子交换色谱将所有分子形式的IgG与所有分子形式的白蛋白分离。第二步，将收集到的IgG部分通过尺寸排阻色谱重新进行色谱分析，并分离成其聚集体、二聚体和单体成分。尽管在此过程中确实会发生一些聚集体的少量损失，但总体分子大小分布并未受到显著影响。所描述的方法既省时又准确，代表了对现有方法的改进。
