Characterization of the glycosylation profile of erythropoiesis-stimulating agents (ESAs) and impact on potency

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2025-08-07 DOI:10.1016/j.jpba.2025.117094

Julie TerWee , Beth McCoy , Bryan Bernat , Kaila Wilson-Landy , Sam Billingham , Krishana Gulla , Catherine Srebalus Barnes

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Abstract

To evaluate the impact of glycosylation of Chinese Hamster Ovary (CHO) cell produced erythropoiesis-stimulating agents (ESAs) on in vivo efficacy, epoetin glycoforms were fractionated and characterized. A comprehensive series of biochemical, in vitro bio-functional analyses and in vivo potency assays were conducted to better understand the relationship of structure to function of epoetin glycoforms. The hyper-glycosylated ESA darbepoetin alfa was also assessed to understand the range of in vivo potency response. Results demonstrate a strong link between sialylation or antennary structure, but not between N-acetyllactosamine repeat number and in vivo potency. Results for darbepoetin as compared to epoetin also confirm an inverse relationship between in vivo potency and potency measured using in vitro methods.

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促红细胞生成素（ESAs）的糖基化特征及其对效力的影响

为评价中国仓鼠卵巢（CHO）细胞产生的促红细胞生成素（ESAs）糖基化对体内药效的影响，对促红细胞生成素糖型进行了分离和表征。我们进行了一系列全面的生化、体外生物功能分析和体内效价分析，以更好地了解促生成素糖型的结构与功能关系。我们还评估了高糖基化的ESA darbepoetin α，以了解体内效价反应的范围。结果表明，在唾液化或触角结构之间有很强的联系，但在n -乙酰乳胺重复数和体内效力之间没有联系。达贝泊汀与依波汀的对比结果也证实了体内效价与体外法测定的效价之间的反比关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.