Determination of degradation for sulfo-SIAB, SM(PEG)2, and sulfo-GMBS by RPLC-UV analysis

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2024-08-30 DOI:10.1016/j.jpba.2024.116455

Melissa Resto, Alison Vinitsky, Nicole A. Schneck, Jeremy J. Wolff, Asif Shajahan, Nicole Cibelli, Yaqiu Zhang, Yile Li, Krishna Gulla, Daniel B. Gowetski, Jason G. Gall, Q. Paula Lei

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引用次数: 0

Abstract

Bi-functional N-Hydroxysuccinimide (NHS) linkers are widely used in the conjugation processes linking an immunogen with a carrier protein capable of boosting immunity. A potential vaccine candidate against HIV-1, called fusion peptide (FP), is covalently linked to the recombinant tetanus toxoid heavy-chain fragment C (rTTHC) via this type of linker. A reversed-phase liquid chromatography (RPLC-UV) method was used to monitor the linker’s degradation kinetics in various buffers, mimicking the steps in the conjugation process. The kinetics of the reactivities of the linkers are revealed in this study and can provide a good guidance to help effective conjugation process before these linkers are completely hydrolyze to the inactive degradants. Three cross-linkers degradation pathways were evaluated: Sulfosuccinimidyl (4-iodoacetyl) aminobenzoate (Sulfo-SIAB), PEGylated SMCC (SM(PEG)₂), and N-γ-maleimidobutyryl-oxysulfosuccinimide ester (Sulfo-GMBS). We have reported kinetics for Sulfo-SIAB.

查看原文本刊更多论文

通过 RPLC-UV 分析确定磺基-SIAB、SM(PEG)2 和磺基-GMBS 的降解情况

双功能 N-羟基琥珀酰亚胺（NHS）连接体被广泛应用于连接免疫原与能够增强免疫力的载体蛋白的共轭过程中。一种名为融合肽（FP）的潜在 HIV-1 候选疫苗就是通过这种连接体与重组破伤风类毒素重链片段 C（rTTHC）共价连接的。采用反相液相色谱法（RPLC-UV）监测连接体在各种缓冲液中的降解动力学，模拟连接过程中的各个步骤。本研究揭示了连接体的反应动力学，可在这些连接体完全水解为无活性降解剂之前为有效的共轭过程提供良好的指导。本研究评估了三种交联剂的降解途径：硫代琥珀酰亚胺基（4-碘乙酰基）氨基苯甲酸酯（Sulfo-SIAB）、聚乙二醇化 SMCC（SM(PEG)2）和 N-γ-马来酰亚胺基丁酰氧基硫代琥珀酰亚胺酯（Sulfo-GMBS）。我们已经报告了 Sulfo-SIAB 的动力学。

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.