A mass spectrometry based functional assay for the quantitative assessment of ABC transporter activity

Rapid Commun Mass Spectrom. 2009 Nov;23(21):3372-6. doi: 10.1002/rcm.4259.

Abstract

ATP-Binding Cassette (ABC) transporters are highly expressed in pharmacological barriers limiting the access of drugs to their targets. Since characterization of a compound as a transporter substrate or inhibitor bears significant consequences in drug development, there is a great need for reliable tools that enable the rapid analysis of the transport susceptibility of drugs. Here we describe a simple but very efficient high-performance liquid chromatography/mass spectrometry (HPLC/MS) assay for measuring the ABC transporter-dependent vesicular transport of compounds. In addition, we provide evidence that the requirement for sample preparation can be minimized using desorption electrospray ionization (DESI)-MS, paving the way for a direct, high-throughput investigation of drug-transporter interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism*
  • Chromatography, High Pressure Liquid / methods*
  • Humans
  • Methotrexate / pharmacokinetics
  • Neoplasm Proteins / metabolism
  • Pharmacokinetics
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Transport Vesicles / metabolism

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Neoplasm Proteins
  • Methotrexate