Characterization of pneumococcal conjugates in vaccine process development by multi-detection hydrodynamic chromatography

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2025-03-20 DOI:10.1016/j.jpba.2025.116826

Xiujuan Jia , James Z. Deng , Michael A. Winters , Mellie June Paulines , Weidong Tong , Erin Cannon , Mirlinda Biba , Ping Zhuang

{"title":"Characterization of pneumococcal conjugates in vaccine process development by multi-detection hydrodynamic chromatography","authors":"Xiujuan Jia , James Z. Deng , Michael A. Winters , Mellie June Paulines , Weidong Tong , Erin Cannon , Mirlinda Biba , Ping Zhuang","doi":"10.1016/j.jpba.2025.116826","DOIUrl":null,"url":null,"abstract":"<div><div>Pneumococcal conjugate vaccines (PCVs) are developed by conjugating pneumococcal polysaccharides to a carrier protein, such as CRM<sub>197</sub>. Size and molecular weight are important attributes of each monovalent conjugate in a PCV, making accurate monitoring of molecular weights crucial during the conjugation process. While size-exclusion chromatography (SEC) coupled with multi-angle light scattering (MALS), refractive index (RI), and ultraviolet (UV) detectors (SEC-MALS) is the gold standard used for absolute molecular weight characterization, this study presents the development of a multi-detection (MALS, UV and RI) hydrodynamic chromatography (HDC-MALS) method and its utility for comprehensive PCV characterization. The optimized HDC-MALS method is employed for in-depth understanding of vaccine conjugation process and effective characterization of heterogeneous, large conjugates through granular molar mass distribution analysis. Compared to other mild separation techniques such as field flow fractionation (FFF), HDC allows for high mobile phase flow rates without compromising separation efficiency, enabling faster run times that meet the demands of in-process control with rapid turn-around times.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"261 ","pages":"Article 116826"},"PeriodicalIF":3.1000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmaceutical and biomedical analysis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0731708525001670","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}

引用次数: 0

Abstract

Pneumococcal conjugate vaccines (PCVs) are developed by conjugating pneumococcal polysaccharides to a carrier protein, such as CRM₁₉₇. Size and molecular weight are important attributes of each monovalent conjugate in a PCV, making accurate monitoring of molecular weights crucial during the conjugation process. While size-exclusion chromatography (SEC) coupled with multi-angle light scattering (MALS), refractive index (RI), and ultraviolet (UV) detectors (SEC-MALS) is the gold standard used for absolute molecular weight characterization, this study presents the development of a multi-detection (MALS, UV and RI) hydrodynamic chromatography (HDC-MALS) method and its utility for comprehensive PCV characterization. The optimized HDC-MALS method is employed for in-depth understanding of vaccine conjugation process and effective characterization of heterogeneous, large conjugates through granular molar mass distribution analysis. Compared to other mild separation techniques such as field flow fractionation (FFF), HDC allows for high mobile phase flow rates without compromising separation efficiency, enabling faster run times that meet the demands of in-process control with rapid turn-around times.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

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.