Polysorbate is one of the most commonly employed non-ionic surfactant in protein containing biological formulations, whereby, it can stabilize these biomolecules under different stress conditions. Despite the fact that polysorbates are present in almost 70% of currently marketed parenteral biological drugs, polysorbate degradation in biopharmaceutical formulations has emerged as a specific quality concern. Different degradation pathways have been explored in the recent years with the aim of understanding the root cause for polysorbate degradation in biopharmaceutical formulations. In an attempt to explore hydrolytic degradation of polysorbates in accelerated degradation conditions, we studied extreme pH conditions. We investigated specific polysorbate degradation profiles depending on acidic or alkaline solution conditions. The acidic and alkaline hydrolysis of polysorbate is monitored for the total content using a fluorescence micelle assay (FMA). Additionally, the compositional changes in polysorbates were detected using reversed phase high performance liquid chromatography coupled to a charged aerosol detector (RP-HPLC-CAD). We show that the stability of polysorbate against chemical hydrolysis is dependent upon selected pH condition and differ for polysorbate 20 and polysorbate 80. Additionally, we were able to show that a degradation pathway dependent fingerprint may support the identification of the degradation root cause.

中文翻译：

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聚山梨酯在水性条件下的酸性和碱性水解：旨在理解生物药物制剂中聚山梨酯的降解。

聚山梨酯是含蛋白质的生物制剂中最常用的非离子表面活性剂之一，因此，它可以在不同的胁迫条件下稳定这些生物分子。尽管在目前市售的肠胃外生物药物中几乎有70％存在聚山梨酯，但生物制药配方中的聚山梨酯降解已成为一个特殊的质量问题。近年来，已经探索了不同的降解途径，目的是了解生物药物制剂中聚山梨酯降解的根本原因。为了探索聚山梨酯在加速降解条件下的水解降解，我们研究了极端pH条件。我们研究了特定的聚山梨酯降解曲线，具体取决于酸性或碱性溶液条件。使用荧光胶束测定法（FMA）监测聚山梨酯的酸水解和碱水解的总含量。另外，使用与带电气溶胶检测器（RP-HPLC-CAD）耦合的反相高效液相色谱法检测聚山梨酯的组成变化。我们表明，聚山梨酯对化学水解的稳定性取决于所选的pH条件，并且对于聚山梨酯20和聚山梨酯80是不同的。此外，我们能够显示依赖降解途径的指纹可能支持对降解根源的鉴定。反相高效液相色谱联用带电气溶胶检测器（RP-HPLC-CAD）检测聚山梨酯的组成变化。我们表明，聚山梨酯对化学水解的稳定性取决于所选的pH条件，并且对于聚山梨酯20和聚山梨酯80是不同的。此外，我们能够显示依赖降解途径的指纹可能支持对降解根源的鉴定。反相高效液相色谱联用带电气溶胶检测器（RP-HPLC-CAD）检测聚山梨酯的组成变化。我们表明，聚山梨酯对化学水解的稳定性取决于所选的pH条件，并且对于聚山梨酯20和聚山梨酯80是不同的。此外，我们能够显示依赖降解途径的指纹可能支持对降解根源的鉴定。