DMPK ADMEtox
Recovery of small molecule drugs from Biological
tissue.
Measurement of small molecule distribution within
model systems is of paramount importance in the area of DMPK / ADME tox.
The high performance sample preparation of Covaris greatly facilitates
this by improving on conventional sample disruption techniques in many
ways and provides a quantitative sample preparation.
Solvay Presentation ADMET 2008
A number of features of AFA in relation to this area are listed below.
| Feature | Benefit |
| Controllable Mechanical Energy | Increased yield (recovery) |
| Isothermal | No heat passed to sample |
| Disrupts all tissue | Ease of use |
| High quality build | Robust |
| Non-Contact | No sample contamination No clean up of instrument post processing Very fast for multiple samples |
| Closed vessel | Safe – no aerosol risk |
| Automated – E series | Large batches can be processed with minimal effort |
To date, a large number of studies
have to date been completed with AFA. In many cases a notable increase in
performance has been observed. This data has been generated by one of the
organizations utilizing the technology. It shows a comparative study of
muscle tissue extraction of a [C14] labeled small molecule. The data illustrates
the increase in performance of AFA compared to conventional Polytron treatment.
[C14] Small molecule drug recovery from muscle tissue
Ease of Use
If a tissue is hard or fibrous then an initial cryo –
pulverisation is required. Use of the Covaris CryoPrep and TissueTube
system greatly facilitates this step (more
details here) by increasing the surface area for the acoustic-based
processes and by enabling the sample to flow into and out of the disruptive
focal zone. The closed vessel TissueTube (TT1) system enables collection,
storage, pulverization, and transfer without touching the sample. This
is especially beneficial for radio-labelled molecules
A typical extraction procedure would comprise :
Add water to a tissue sample, seal, and place the capped
tube into the instrument. The instrument is then activated and the homogenisation
started. Typical homogenisation times are 30seconds – 1min. The
sample is then extracted by adding an organic solvent and the total dpm
in the supernatant determined.
If the E-200 instrument is used then up to 96 samples can be automatically processed in a single operation, greatly increasing throughput over conventional techniques. Sample number is determined by sample mass. Alternatively, the S2 system can process a single sample.
This time-lapsed video isa 45 second process
(video include time gaps).