Alan Barnes (Presenter)
Shimadzu
Bio: As LCMS Applications Research Scientist I work with a diverse range of topics with method development in clinical, forensic and toxicology analysis in addition to targeted proteomics and metabolomics. At MSACL we are presenting drug screening in collaboration with the University of Limoges.
Authorship: Alan Barnes (1), Tiphaine Robin (2), Neil Loftus (1), Pierre Marquet (2), Sylvain Dulaurent (2), Franck Saint-Marcoux (2)
(1) Shimadzu Corporation, Manchester, UK (2) CHU Limoges, France
| Short Abstract Forensic and toxicological drug screening has a number of challenges with the need for rapid sample analysis and reporting with quantitative results. Multi Target Screening (MTS) methods were developed using multiple reaction monitoring (MRM) with threshold triggered MS/MS product ion scans at three collision energies to enable spectral based library searching. The MS/MS library was created using certified reference materials and included electrospray spectral data on over 1200 compounds relevant to clinical and forensic toxicology in both positive and negative ion modes. These experiments were applied to reduce false positive and negative reporting using MS/MS spectral library based identification. |
Long Abstract
Forensic and toxicological drug screening has a number of challenges with the need for rapid sample analysis and reporting with the need for quantitative results. The challenge of modern screening analyses is to measure toxicologically high concentrations with the expectation of forensic low limits of detection also being possible. In these experiments, Multi Target Screening (MTS) was applied to systemic toxicological analysis to reduce false positive and negative reporting using MS/MS spectral library based identification. MTS methods were developed using multiple reaction monitoring (MRM) with threshold triggered MS/MS product ion scans at three collision energies to enable spectral based library searching. The MS/MS library was created using certified reference materials and included electrospray spectral data on over 1200 compounds relevant to clinical and forensic toxicology in both positive and negative ion modes. The MTS approach was applied to screening samples in a routine clinical toxicology environment.
MTS methods were developed to screen whole blood spiked with a range of commonly observed compounds including antidepressant compounds, anxiolytic drugs, analgesics and antipsychotic agents. Samples were prepared by QuEChERS method with inclusion of internal standard compounds to normalise sample matrix effects. Analysis was performed by reversed phase UHPLC separation (Nexera LC, Shimadzu Corporation using a Restek Biphenyl 2.7um 2.1x100mm column) followed by MRM triggered product ion scan MS/MS (LCMS-8060, Shimadzu Corporation). Data analysis was performed using LabSolutions Insight software utilising the spectral library containing over 1200 compounds.
The approach of using MRM triggered product ion spectra to detect and identify a panel of compounds commonly found in clinical and forensic toxicology was applied to whole blood samples spiked at a concentration range between 2.5-100ug/L. All compounds were detected and positively identified using product ion scan MS/MS with library based searching generating higher data quality for compound identification. As the MS/MS library was acquired using a broad range of collision energies from 10 to 55eV and merged into a single information-rich reference spectrum, the library matching process resulted in a high confidence in compound identification and reporting. This approach also resulted in quantitative data with regression coefficients (r2) greater than 0.99 for compounds within the panel. Screening methods were successfully tested using high, medium and low spiked whole blood (500, 100, 20ug/L) to test clinically relevant concentrations in screening work flows.
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