Novel markers to track oxidative polysorbate degradation in pharmaceutical formulations

被引：31

作者：

Dahotre, Sanket ^{[1
]}

Tomlinson, Anthony ^{[1
]}

Lin, Baiwei ^{[2
]}

Yadav, Sandeep ^{[1
]}

机构：

[1] Genentech Inc, Late Stage Pharmaceut Dev, 1 DNA Way, San Francisco, CA 94080 USA

[2] Genentech Inc, Discovery Chem, 1 DNA Way, San Francisco, CA 94080 USA

来源：

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 2018年 / 157卷

关键词：

Biopharmaceutical formulations; Polysorbate; 20; Oxidative degradation; Fatty acid esters; 2,4-Dinitrophenylhydrazine; Reverse phase ultra high performance liquid chromatography; FATTY-ACID PARTICLES; MASS-SPECTROMETRY; BIOPHARMACEUTICAL FORMULATIONS; ALLERGENIC ACTIVITY; SURFACTANTS; IDENTIFICATION; HYDROLYSIS; STABILITY; ALDEHYDES; PRODUCTS;

D O I：

10.1016/j.jpba.2018.05.031

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Polysorbates can undergo oxidative degradation in pharmaceutical formulations resulting in both soluble and insoluble degradation products. The insoluble degradants may precipitate to form subvisible and visible particulates, which are undesirable in liquid parenteral products. To date, no oxidation byproduct has been identified as an established marker to track Polysorbate 20 oxidation. Herein, we identified the aldehyde derivative of free fatty acid esters as a byproduct of polysorbate oxidation that can be derivatized using 2,4-dinitrophenylhydrazine and tracked analytically to monitor oxidative polysorbate degradation in pharmaceutical formulations. (C) 2018 Elsevier B.V. All rights reserved.

引用

页码：201 / 207

页数：7

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