Mass Spectrometry of Human Transporters

Brahim Achour, Zubida Al-Majdoub, Amin Rostami-Hodjegan, Jill Barber
2020 Annual Review of Analytical Chemistry  
Transporters are key to understanding how an individual will respond a particular dose of a drug. Two patients with similar systemic concentrations may have quite different local concentrations of a drug at the required site. The transporter profile of any individual depends upon a variety of genetic and environmental factors, including genotype, age, and diet status. Robust models (virtual patients) are therefore required and these models are data hungry. Necessary data include quantitative
more » ... nsporter profiles at the relevant organ. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is currently the most powerful method available for obtaining this information. Challenges include sourcing the tissue, isolating the hydrophobic membrane-embedded transporter proteins, preparing the samples for MS (including proteolytic digestion), choosing appropriate quantification methodology, and optimizing the LC-MS/MS conditions. Great progress has been made with all of these, especially within the last few years, and is discussed here. Expected final online publication date for the Annual Review of Analytical Chemistry, Volume 13 is June 12, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
doi:10.1146/annurev-anchem-091719-024553 pmid:32084322 fatcat:xdczamqzcja4jg6gtdamebvdlq