The Role of Chromatography in Bioanalytical Studies

The accurate determination of the concentration of a drug candidate and it’s resulting metabolites in biological fluids plays an essential in the drug discovery, preclinical and clinical development programs. The drug concentration values determined are used to calculate the pharmacokinetics properties of the candidate drug molecules; such as Area Under the Curve (AUC), T 1/2, Cmax and elimination constant. In discovery these values are used to select the most promising candidate compound, from a library or parallel synthesis experiment, to be carried forward into development.

In development the pharmacokinetic values derived from both DMPK and safety assessment studies are used to provide evidence of the dosed compound exposure, (in safety assessment studies) evaluate the effect of increased drug dosing on compound exposure and estimate the appropriate dose to be used in the initial human clinical trails. At this point the metabolism of the compound in mammalian species, such as rat, dog and mouse is also extensively studied and accurately defined.

Again this requires the accurate measurement of drug and metabolite concentrations; normally performed using a radio labelled isotope of the drug. During the initial phase I clinical studies the derived drug concentration values are used to determine the pharmacokinetics and exposure of the drug in health human volunteers. As these values are used to measure the effect of increased exposure to the drug and give guidance to the clinical team with respect to the next dose, rapid assay turnaround is required to deliver results in a 24 hour time period or less. As the early dosing in man is at extremely low levels the assay must have sufficient sensitivity to accurately determine the elimination phase of the pharmacokinetics curve if correct values for half-life, AUC and elimination constant are to be determined.