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Increasing the Speed of ADME Screening using Quantitative High Resolution Accurate Mass Spectrometry

Most laboratories, including our own, use standard triple quadrupole mass spectrometers to analyse samples generated by ADME screens. On these systems, up-front optimisation of the compounds is required prior to sample analysis. This can lead to bottlenecks when screening large numbers of compounds and delay the analysis of the samples from the ADME assays.

Major advances have been made in recent years in the field of high resolution accurate mass spectrometry, enabling both highly quantitative and in-depth qualitative analytical data to be collected from a single injection. Furthermore, these instruments require little or no up-front optimisation prior to sample analysis, allowing turnaround time for assays to be reduced and efficiency in the laboratory to be improved. A key advantage of these systems is that additional data can be collected from the same injection. This is especially important in the case of metabolic stability assays where not only can the system be used to quantify parent compound disappearance and intrinsic clearance but can also collect initial information on the metabolites formed in the incubations. The volume of data generated can be large and a strategy needs to be designed for storing and deleting data efficiently.

Cyprotex have recently installed two Sciex TripleTOF® instruments at its facilities and are now utilising this platform for analysing samples from microsomal and hepatocyte stability incubations for one of its clients. Data handling can be facilitated in a semi-automated way by commercial (DiscoveryQuant™) software or in a fully automated manner using an in-house developed software which automates the process and allows smooth integration into our internal LIMS.

Cyprotex currently runs up to 8000 samples per day through our mass spectrometers in the UK. We feel that utilising this technology in the future will enable us to operate more efficiently and deliver data more quickly to our clients.

At the recent DMDG /GMP Open Meeting in Paris on 19-21 October 2016, Sciex presented a poster titled ‘High throughput screening ADME-Tox: Transitioning from triple quadrupole to high resolution accurate mass spectrometry’. Cyprotex provided the assay samples for the work described in the poster and have subsequently developed an in-house automated workflow for data processing and interfacing with our LIMS.

Download the poster.

 

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