Pharmacokinetics and bioanalysis

Pharmacokinetic Analysis

Pharmacokinetics (PK) is the study of what the body does to drugs. It is the mathematical study and description of the absorption, distribution, metabolism, and excretion processes used by the body when a drug is administered. To obtain good PK data, bioanalysis forms an integral part of the process as it is essential to accurately quantify levels of drug in the body over a period of time.  

For pharmacokinetic analysis, the Core Facility has Certara Phoenix (formerly Pharsight WinNonLin®) software, the industry standard software for compartmental and non-compartmental PK analysis. Phoenix® also has the capability to simulate the time-concentration profile to establish the effect of changing dose, dose schedule, or dose route.  

Regulated Bioanalysis

Regulated bioanalysis is the application of bioanalytical methods to measure drug concentrations and biomarkers in biological samples under strict quality standards.  These include ensuring clinical sample integrity, data integrity, patient safety, and confidentially requirements.

The Core Facility works to the MHRA’s guidelines for Good Clinical Practice for the Clinical Laboratory (often abbreviated to GC(L)P) and is therefore able to support the analysis of samples from clinical trials. The bioanalytical methods we use are fully validated following the ICH Harmonised Guideline on Bioanalytical Method Validation and Study Sample Analysis, M10. We also store and track the samples in compliance with the Human Tissue Authority (HTA) regulations using the Achiever Medical LIMS system.

Drug Discovery

Drug candidate selection is the process of identifying the best molecules that can be developed into a new treatment for a specific disease or illness. Working closely with the BRU Core, with a depth of experience in drug administration to mouse models of cancer, our home office licence allows us to conduct in vivo studies in mice using three different protocols.

The three types of drug discovery studies we can offer are: discovery pharmacokinetics (initial pharmacokinetics), dose optimisation (maximum tolerated dose) and drug efficacy studies.

Metabolomics

Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the “systematic study of the unique chemical fingerprints that specific cellular processes leave behind”, the study of their small-molecule metabolite profiles. Metabolic profiling can give an instantaneous snapshot of the physiology of that cell, and thus, metabolomics provides a direct “functional readout of the physiological state” of an organism.

In cancer cells, metabolism is dysregulated to support the demands of uncontrolled proliferation. This rewiring of cellular metabolism leads to characteristic metabolic phenotypes that can be used for earlier cancer diagnosis, patient selection strategies for clinical trials, and/or as biomarkers of treatment response. Altered metabolism also results in unique metabolic dependencies that, in some cases, can be targeted with precision medicine and nutrition, including drugs that selectively target metabolic enzymes.

We can quantify a large number of metabolites in a single assay and have methods set up for many common organic endogenous molecules and amino acids. The method is being constantly updated to include new analytes.

Analytical quantitation

We specialise in developing and running bioanalytical assays, that is: extracting small molecules from biological samples and quantifying these small molecules by liquid chromatography-mass spectrometry (LC-MS/MS). The molecular mass ranges we operate range between 50 and 2000 amu (atomic mass units), if it is any larger, then the Proteomics Core could be an alternative option. We have developed over 130 validated methods.

Drug formulation

Many new chemical entity (NCE) that are being investigated are poorly soluble, thus need to be combined with inactive ingredients, to ensure adequate solubility and bioavailability when they are administered to mice.  We offer a drug formulation service used in conjunction with our drug discovery service, to prepare suitable dose solutions which are safe to administer to mice.

We also offer a dose solution verification service, to evaluate the concentration of a dose solution prepared by research groups.