Mapping pharmaceuticals in tissues using MALDI imaging mass spectrometry.
During drug discovery and development stage, often the question is raised as to whether the drug can reach the site of action which helps researchers better assess the potential value of that compound as a pharmaceutical product and toxicological outcomes. High performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS) has totally replaced HPLC methods that use UV or other detectors for most drug analysis applications. However, HPLC-MS/MS approaches are not able to provide the answer to certain questions regarding the distribution of a drug in various organs or tissues from laboratory animal experiments. Whole body radioautography (WBA) normally provides a standard means to answer this question on the time course of the drug candidates. However, the major disadvantage in this radioautographic technique is to allow for visualization of total drug-related materials but to image the distribution of the administrated drugs and their metabolites in all tissues. In addition, the availability of radiolabeled compounds at drug discovery stage is another concern. To overcome these issues, matrix-assisted laser desorption/ionization-mass spectrometric method (MALDI-MS) has been developed to directly determine the distribution of pharmaceuticals in tissue sections which might unravel their disposition or biotransformation pathway for new drug development.
Hsieh
Yunsheng
Y
Drug Metabolism and Pharmacokinetics Department, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. yunsheng.hsieh@spcorp.com
Chen
Jiwen
J
Korfmacher
Walter A
WA
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D051379:Mice; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000378:metabolism*; D010599:Pharmacokinetics; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D004364:Pharmaceutical Preparations