Drug metabolite quantitation and identification is critical to drug discovery and development. In discovery, knowledge of the metabolic site(s) of drug candidates is essential for selecting compounds with favorable PK properties and helps medicinal chemists modify metabolic soft spots. This increased emphasis on obtaining ADME/PK data on large numbers of discovery candidates has placed greater demands on throughput and reproducibility of ADME/PK assays. Automated liquid handling and sample preparation, as well as, high throughput analytical technologies are a key part of the instrumentation arsenal of modern Discovery ADME/PK laboratories.
In development, elucidation of biotransformation pathways of drug candidates is vitally important to understanding physiological effects and potential toxicity. Additionally, current regulatory guidance re-emphasizes the role of drug metabolite identification and quantitation.
Monitoring a drug candidate as well as its metabolites from a variety of biological matrices makes for a very challenging analysis. In addition, drug lead compounds may have one or multiple chiral centers and their oxidative metabolism may further result in new stereo-centers. These isomers may be formed with different abundances and hence quantifying each individual isomeric metabolite is important. One extremely powerful approach to resolving stereoisomeric metabolites of close physicochemical properties, is to resolve them using chromatographic techniques ahead of mass spectrometric analysis. Our customers have been successful at solving the most complex of bioanalytical challenges by complementarily using UHPLC, 2D LC, SFC, high-resolution Q-TOF mass spectrometry and high sensitivity triple quadrupole mass spectrometry.
Whether it is increased throughput and automation that is needed in your discovery ADME/PK laboratories or cutting-edge chromatography coupled to robust and reliable mass spectrometry in your development bioanalytical laboratory, Agilent has the right solutions for your every need.