DMPK is an essential part of early drug discovery

The primary goal of the evolving drug discovery landscape in pharma and biopharma is minimising the attrition rate of drug candidates in the drug discovery pipeline. Drug metabolism and pharmacokinetic (DMPK) profiles of prospective new drugs must be evaluated for properties such as bioavailability, half-life, clearance and metabolic profile. A sub-optimal DMPK profile is a key cause of the discontinuation of drug leads, as well as unwanted side effects.

The goal of DMPK studies in drug discovery is to screen multiple compounds, evaluate their intrinsic DMPK properties, and then perform additional metabolism studies on a subset of compounds likely to proceed to drug development. Therefore, an understanding of drug candidate metabolic profiles is essential to the selection of compounds with desirable DMPK properties in early drug discovery.

In recent drug discovery history, there has been a push to assess DMPK-related parameters earlier on in the discovery pipeline. Research and development labs are focussing on designing molecules with a high drug target affinity, low clearance and high oral bioavailability and optimal metabolic characteristics. In response, DMPK studies are integrated in earlier stages of drug discovery and therefore, the throughput capabilities of both pharmacokinetics and in vitro metabolism assays have increased dramatically.

Liquid chromatography tandem mass spectrometry (LC-MS/MS) allows high throughput and high sensitivity analysis of samples for increasingly large numbers of compounds, therefore increasing the number of drug candidates progressing through the drug discovery and development pipeline. LC-MS/MS is the technique of choice for researchers conducting DMPK studies, and mass spectrometry imaging (MSI), originally developed for protein and peptide analysis, has recently been extended to DMPK using MALDI-MS. MALDI Imaging  enables research labs to visualise drugs and metabolites in tissue, enabling differentiation between drug compounds and their metabolites.