TY - JOUR
T1 - Mass Spectrometry of Human Transporters
AU - Achour, Brahim
AU - Al-Majdoub, Zubida
AU - Rostami-Hodjegan, Amin
AU - Barber, Jill
PY - 2020/6/12
Y1 - 2020/6/12
N2 - 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 transporter 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.
AB - 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 transporter 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.
U2 - 10.1146/annurev-anchem-091719-024553
DO - 10.1146/annurev-anchem-091719-024553
M3 - Article
SN - 1936-1327
VL - 13
SP - 223
EP - 247
JO - Annual Review of Analytical Chemistry
JF - Annual Review of Analytical Chemistry
ER -