The measurement of small molecule distributions, within model systems, is of paramount importance in the area of DMPK / ADME/Tox. The high performance sample preparation of Covaris greatly facilitates this process by improving the conventional sample disruption techniques in many ways and provides quantitative sample preparations.

Using the Covaris AFA™ sample preparatory process, the analytical performance of various instruments (such as mass spectrometers) involved in the measurement of drug metabolic distribution can be enhanced. Potential benefits include the following:

• Eliminate variation from sample preparation
• Ascertain the degree of variation from the tissue
• Recovery of small molecule drugs from Biological tissue

A number of features of AFA in relation to this area are listed below.

Feature	Benefit
Controllable mechanical energy	Increased yield (recovery) Sample prep variation is eliminated Greater precision than other conventional techniques (reduced CV) Highly reproducible
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 No sample cross talk No clean-up, nor decontamination
Automated – E series	Large batches can be processed with minimal effort

Ease of Use

The CryoPrep™ and TissueTube system greatly facilitates this step by increasing the surface area for the acoustic-based processes, and by enabling the sample to flow in and out of the disruptive focal zone. The closed vessel TissueTube (TT1) system enables rapid collection, storage, pulverization, and transfer without touching the sample. This is especially beneficial for radio-labeled 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 homogenization is started. A typical duration of homogenization is between 30 and 60 seconds. The sample is then extracted by adding an organic solvent and the total dpm in the supernatant determined.

Using the E-series instruments, 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.