Quantitative whole-body autoradiography, LC-MS/MS and MALDI for drug-distribution studies in biological samples: the ultimate matrix trilogy.
The drug-development process requires an understanding of the ADME properties of the novel therapeutic agent. Determination of drug concentrations and identity in excreta (urine and feces) examines the products of these processes. Similar measurements made on plasma, while accurately determining exposure, show only what is being transported around the body. Both activities fail to confirm the nature of components at the pharmacologically relevant matrix - the tissue. Attention is therefore being directed towards methods that can be employed to address this lack in our current methodologies, to provide better quality data on which risk assessments can be made, so that pharmacological models can be refined, and drug safety improved. In this article, we will look at the current methods used to obtain tissue drug and drug metabolite concentrations, and their potential use in drug discovery.
Department of Metabolism, Quotient Bioresearch Ltd, Pegasus Way, Rushden, NN10 6ER, UK.
Andrew B
AB
McEwen
Claire M
CM
Henson
Stuart G
SG
Wood
D000818:Animals; D001345:Autoradiography / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution; D014916:Whole-Body Irradiation / Q000379:methods*
D004364:Pharmaceutical Preparations