Pharmacokinetic and metabolic analysis of an Alzheimer's disease therapeutic in rat serum via microfluidic CZE–MS

Zachary D. Kelley, Mark A. Lovell, Bert C. Lynn

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Sensitive, high-throughput methods for pharmacokinetic (PK) profiling are essential for potential therapeutics during critical stages of clinical trials. The application of a microfluidic capillary zone electrophoresis mass spectrometry (CZE–MS) method for PK profiling allows for rapid, sensitive and in-depth analysis of multiple samples within a short timeframe. Here, a CZE–MS approach for PK analysis was compared with a traditional UHPLC–MS approach when analyzing serum extracts from rats treated with a potential Alzheimer's disease therapeutic, BNC-1. Resulting PK data generated from both methods displayed statistical similarities. Additionally, the separation efficiency attributed to the use of the CZE–MS method provided substantial metabolic regulation data that was not apparent in the UHPLC–MS method. Additionally, the coupling of the CZE–MS method to the data processing software, MZmine2, was used to monitor changes in metabolism and observe putative BNC-1-derived metabolites. The ability to perform fast analyses without sacrificing sensitivity or metabolic information suggests that this CZE–MS method is ideal for metabolomics-inclusive, high-throughput PK profiling.

Original languageEnglish
Article numbere5243
JournalBiomedical Chromatography
Volume36
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Publisher Copyright:
© 2021 John Wiley & Sons, Ltd.

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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