Measuring Drug Metabolism Kinetics and Drug-Drug Interactions Using Self-Assembled Monolayers for Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry

Lyndsey L. Anderson, Eric J. Berns, Pradeep Bugga, Alfred L. George*, Milan Mrksich

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The competition of two drugs for the same metabolizing enzyme is a common mechanism for drug-drug interactions that can lead to altered kinetics in drug metabolism and altered elimination rates in vivo. With the prevalence of multidrug therapy, there is great potential for serious drug-drug interactions and adverse drug reactions. In an effort to prevent adverse drug reactions, the FDA mandates the evaluation of the potential for metabolic inhibition by every new chemical entity. Conventional methods for assaying drug metabolism (e.g., those based on HPLC) have been established for measuring drug-drug interactions; however, they are low-throughput. Here we describe an approach to measure the catalytic activity of CYP2C9 using the high-throughput technique self-assembled monolayers for matrix-assisted laser desorption-ionization (SAMDI) mass spectrometry. We measured the kinetics of CYP450 metabolism of the substrate, screened a set of drugs for inhibition of CYP2C9 and determined the Ki values for inhibitors. The throughput of this platform may enable drug metabolism and drug-drug interactions to be interrogated at a scale that cannot be achieved with current methods.

Original languageEnglish (US)
Pages (from-to)8604-8609
Number of pages6
JournalAnalytical Chemistry
Volume88
Issue number17
DOIs
StatePublished - Sep 6 2016

ASJC Scopus subject areas

  • Analytical Chemistry

Fingerprint Dive into the research topics of 'Measuring Drug Metabolism Kinetics and Drug-Drug Interactions Using Self-Assembled Monolayers for Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry'. Together they form a unique fingerprint.

  • Cite this