Ludwig-Maximilians Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Butenandtstraße 5-13, 81377 Munich, Germany.
Bayer AG, Pharmaceuticals, Formulation Development Parenterals, Friedrich-Ebert-Str. 475, 42096 Wuppertal, Germany.
J Pharm Sci. 2021 Nov;110(11):3541-3545. doi: 10.1016/j.xphs.2021.07.012. Epub 2021 Jul 22.
Tunable resistive pulse sensing (TRPS, qNano Gold, IZON Ltd.) was investigated as a method to quantify submicron particles (SMPs) between 0.1 and 1 µm in solutions of biopharmaceuticals. To reduce sample dilution, a spiking-in approach was used to add the appropriate amount of electrolytes required for the measurement. For correct particle quantification, an electrolyte concentration of at least 50 mM sodium chloride was needed. Intra- and inter-nanopore variability were below 5% for size and below 10% for concentration measurements when analyzing polystyrene standard beads. Submicron particle counts in a stir stressed IgG1 monoclonal antibody formulation resulted in a non-symmetrical, almost bell-shaped size distribution with a maximum at 250 nm when using a NP300 nanopore (IZON Ltd.). It was shown that particle counts are heavily underestimated below 250 nm, and therefore it is recommended to quantify particle counts by TRPS in samples with heterogeneous particle size distributions (e.g., biopharmaceuticals) only starting from the maximum of the histogram towards the upper limit of detection.
可调电阻脉冲感应（TRPS，qNano Gold，IZON 有限公司）被研究用于定量生物制药溶液中的亚微米颗粒（SMPs），粒径范围为 0.1-1μm。为了减少样品稀释，采用了添加法来加入测量所需的适量电解质。为了正确进行颗粒定量，至少需要 50mM 的氯化钠电解质浓度。当分析聚苯乙烯标准珠时，大小的内孔和内孔间变异性低于 5%，浓度测量的变异性低于 10%。在搅拌应激 IgG1 单克隆抗体制剂中进行亚微米颗粒计数时，使用 NP300 纳米孔（IZON 有限公司）时，粒径分布呈非对称的、几乎钟形，最大值在 250nm 处。结果表明，粒径低于 250nm 时的颗粒计数严重低估，因此建议在具有不均匀颗粒粒径分布（例如生物制药）的样品中，仅从直方图的最大值开始，向检测上限方向，通过 TRPS 进行颗粒计数。
