LC–MS based large molecule bioanalysis in drug screening and preclinical pharmacokinetics

Protein quantitation by LC–MS has become an increasingly popular field in the drug discovery phase. In WuXi AppTec (Shanghai, China), we have set up a general workflow for the quantitation of large molecules with LC–MS, where smaller proteins will be analyzed with high-resolution MS by the intact approach and larger proteins will be analyzed by the surrogate peptide approach.

In order to reduce interference, increase sensitivity and improve sample-preparation efficiency, novel functionalized membrane immunoaffinity purification has been introduced, which could reduce immunoaffinity purification time from hours to minutes. Direct tryptic digestion, Protein A functionalized magnetic beads and Protein A membrane sample-preparation methods have been developed, validated and applied in a rat pharmacokinetics study.


What will you learn?

  • Overview of large molecule bioanalysis with LC–MS
  • Intact approach for the quantitative and qualitative analysis of large molecules
  • Surrogate peptide approach for the quantitative bioanalysis of large molecules
  • Novel immunoaffinity purification method


Who may this interest?

  • Bioanalytical scientists
  • Scientists working on protein bioanalysis
  • Key decision makers for preclinical and clinical outsourcing of bioanalytical programs
  • CROs



Zhiyu Li

Zhiyu Li
Associate Director and Principle Scientist
DMPK Department, Lab Testing Division, WuXi AppTec (Shanghai, China)

Dr Zhiyu Li is an Associate Director and Principle Scientist of WuXi AppTec. She leads the New Capability Building Team in the non-GLP Bioanalysis Unit of the DMPK Department. She got her BSc in chemistry from Peking University (Beijing, China) and PhD in analytical chemistry from Indiana University Bloomington (IN, USA). Currently, her job focus is on building new capabilities and platforms, especially for the quantitative bioanalysis of large molecules for drug screening and preclinical DMPK.


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