PK and Bioanalysis
Sygnature Discovery offers a dedicated team and complete support to pharmacokinetics, bioanalysis and metabolite identification which is adapted to each project needs. Our vast experience is complemented with a suite of state-of-the art dedicated bioanalytical and metabolic identification mass spectrometry equipment.
Pharmacokinetics evaluation is required during the drug optimisation phase to inform projects of in vivo disposition of lead candidates. Typically, the first in vivo experiment during an oral drug discovery project would be a single IV bolus dose in a preclinical species. Usually, the compounds are first tested in rodent species followed by non-rodent studies as the programme approaches a preclinical candidate selection. This discipline describes the relationship between drug concentration and time in an organism following administration.
- IV bolus study allows the determination of key PK parameters such as AUC, Cmax, t½, Vss and clearance.
- After a test compound has successfully passed this first PK hurdle, further PK studies are used to build a more detailed picture of all aspects of ADME.
- Oral PK, in combination with the above IV data allows the determination of oral bioavailability (F). Low oral Bioavailability can be caused by poor absorption and/or high first-pass metabolism.
- Collection of urine or bile allows calculation of renal and biliary clearance and identification of metabolites.
Sygnature Discovery offers state-of-the-art non-GLP bioanalysis using matrix-matched calibration curves to deliver a full quantification of unknown samples. For most drug discovery applications, our UPLC-MS/MS services allow rapid, accurate and sensitive quantification from a wide variety of biological matrices.
- Using ultra high performance liquid chromatography (UHPLC) on a range of different columns provides a significant improvement in resolution and throughput over conventional high performance liquid chromatography (HPLC) and combining this with tandem mass spectrometry (MS/MS) as the detector guarantees excellent specificity and sensitivity.
- This allows the bioanalysis of a wide range of compounds from very small polar molecules using hydrophilic interaction liquid chromatography (HILIC) to more conventional drug-like molecules and peptides.