EU-ToxRisk is a European collaborative project funded by the EU framework programme for research and innovation, Horizon 2020. The aim of the consortium is to drive a paradigm shift in toxicological testing away from animal testing and towards a human toxicological assessment based on human cell responses and a comprehensive mechanistic understanding of chemical adverse effects. The focus of the project is predominantly chemicals rather than pharmaceuticals. On occasion, these molecules can present analytical challenges and traditional LC-MS/MS may not be suitable, especially for those with small molecular weights and a lack of ionisable groups.
Cyprotex is one of the partners contributing to the in vitro ADMET data required for the project – this includes metabolic stability assessment using human hepatocytes, Caco-2 permeability testing and protein binding assessment. Amongst the chemicals to be tested were 2,4-dimethyl phenol, tert-butyl-hydroquinone, phenol and PCB 180. Sensitivity of these compounds was limited by traditional LC-MS/MS and so an APGC-MS method was developed to improve the limit of detection and allow the ADME parameters to be determined. To achieve this, processing of the samples had to be adapted to be compatible with the GC-MS analysis.
For the project, Cyprotex utilised a Waters Xevo QTof G2-S system with an APGC interface combining enhanced sensitivity with improved matrix tolerance and quantitative performance. Using this analytical approach, Cyprotex were able to extend the range of chemicals that could be analysed over LC-MS/MS alone.
This work was presented at the 38th BMSS Annual Meeting in Manchester on the 5-7th September 2017.
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