Magazine Integrating Biology and Chemistry for De… – Genetic Engineering & Biotechnology News

Current Tools

Traditional approaches and tools available for the risk assessment of safe and efficacious drugs have been based on measuring the parent drug in plasmaboth in animal models and humans. This often does not provide a sufficient level of information to the scientist. It is recognized that most drug targets are not in plasma, and determining the relevant tissue distribution of not only the parent drug but also its metabolites would provide much greater understanding of pharmacology and toxicology.

The current best practice methods of quantitative whole body autoradiography (QWBA) and liquid chromatography-mass spectrometry (LC-MS) put the emphasis on tissues rather than plasma, but still fall short of providing the complete picture. Both techniques have challenges. QWBA is the technique of choice for determining drug distribution,1 and the data generated is often primarily provided in new drug regulatory submissions. The technique, however, presents a composite of the total radioactivity present and cannot distinguish parent drug from metabolite. Thus it has severe limitations for researchers looking for insight into biochemical pathways and mechanisms.

LC-MS analysis is performed on extracts from tissue homogenates. This type of analysis does not elucidate any spatial information and, just as importantly, can be misleading. For example, if an analyte in the tissue is highly localized, the homogenization process could potentially dilute it below the limit of detection (LOD). Alternatively, when an analyte is determined from tissue homogenate, a researcher could draw incorrect conclusions about toxicity, because the analyte is presumed to be evenly present throughout the tissue when in fact it may be highly localized.

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Magazine Integrating Biology and Chemistry for De... - Genetic Engineering & Biotechnology News