Drug metabolism (DM), pharmacokinetic (PK) and toxicokinetic (TK) studies provide crucial insight into how drug candidates behave in the body and are critical steps in drug development.
- Lower blood volumes (10–20μL/sample)
- Simpler processing: Three-step DBS procedure more straightforward than the cumbersome centrifugation, isolation and clean up of plasma
- Easy storage and transport, room temperature stability save on cost of dry ice shipments
These types of analysis require large volumes of blood (100–500μL per subject per time point) to provide sufficient plasma volume for quantitative bioanalysis. Because only a limited blood volume can be drawn from each animal the number of serial samples is restricted and composite sampling must be used. This use results in lower quality PK data and an increase in the number of animals required. The large volumes make it difficult to conduct studies in juvenile subjects. Plasma needs to be isolated from whole blood and prepared for bioanalysis using solid phase extraction, liquid-liquid extraction or protein precipitation. This time-consuming process limits throughput and consequently how many samples can be tested. There are practical challenges with shipping and storing blood samples, that require controlled handling and frozen transportation and storage.
The dried blood spot (DBS) method is an alternative technique that overcomes these drawbacks. DBS microvolume sampling using specialised media has been shown to be both precise and accurate for a variety of compounds from different structural classes with acceptable inter- and intra-assay variability. It is now being routinely employed in PK/TK studies. The FTA DMPK-A and FTA DMPK-B cards lyse cells and denature proteins on contact. FTA DMPKC card is not impregnated with chemicals and may be better suited for protein-based biomolecules. The choice of DMPK card depends on many factors, such as the analyte chemical structure, extraction solvent and analysis workflow. The final decision is determined empirically.
Samples can be shipped and stored at ambient temperature and long-term stability has been demonstrated for analytes and metabolites sensitive to plasma enzymes.
