Agilent and BioTrove push discovery efficiency

The initial co-marketing agreement will see the two companies collaborating to deliver ultra high-throughput systems that will enable a 384 well-plate to be purified and analysed in around 40 minutes compared to an estimated 20 hours using traditional LC/MS (liquid chromatography mass spectrometry) techniques.

The system combines BioTrove's RapidFire high-throughput sample preparation system with Agilent's 6410 Triple Quadrupole mass spectrometer.

The RapidFire system that removes the need for any front-end processing of samples by using an automated microfluidics platform that separates compounds of interest from the bulk biological material used in drug discovery and ADME (absorption desorption metabolism and excretion) screening programs.

When combined with Agilent's triple quadrupole MS the companies claim that the system can reliably detect compounds with femtogram (1x10 -21 kg) sensitivity.

The system doesn't come cheap with the US list price for the RapidFire system set at $295,000 (€207,000) and the 6410 triple quadrupole MS at $223,000.

However, the companies believe that the time savings and increased throughput will quickly overshadow the upfront costs, "One of our clients has told us that the RapidFire system has paid for itself in the just a couple of weeks," said Dr Selena Larkin, director of RapidFire business development at BioTrove.

"Rather than having to resort to fluorescence technologies that have inherent problems with background, lack of specificity and photobleaching, researchers are now able to use the gold standard of MS earlier in the drug development process and get very good quality data in a screening-friendly time-frame."

The companies believe that the primary use of the system will be in early ADME stages of research when researchers need to check that drug candidates do not affect the metabolism of common over the counter drugs by cytochrome P450 liver enzymes.

Because the triple quadrupole MS can be 'tuned' to find signals from the drugs and their metabolites, unlabelled drug probes can be used rather than needing to develop fluorescently labelled assays.

This dramatically speeds up the screening process and enables these screens to be carried out earlier in the process to remove those candidates that have unwanted ADME profiles.

"The MS analysis system suppresses false positives and negatives caused by artefacts generated using fluorescence assay systems," said Dr Michael Frank, product manager pharmaceutical solutions at Agilent.

"This increases the efficiency of the overall drug development process by reducing the chance that researchers are misled by results and waste time developing the wrong compounds."

BioTrove has already used the system to screen over 3 million samples for clients in primary screens for otherwise intractable drug targets and these early-stage ADME screening.

In addition, BioTrove states that the earlier incarnation of the RapidFire system is in use by 10 of the top 15 pharmaceutical companies.

According to Dr Larkin, the system will also find use in the primary screening for new targets as well an orthogonal screening method to validate results from more traditional fluorescence or colourmetric high-throughput methods.

"The system is incredibly flexible and can also be used in ligand-binding and ligand-displacement studies as well as for testing the metabolic stability of drug candidates," said Dr Larkin.

"This partnership with Agilent will enable us to take these complex analytical tools and apply them to the biological marketplace, making this technology much more available."