Projects

Project IS8 - Traceable Measurement of Vanadium-containing Biomolecules

Background

LGC has become a recognised world leader in elemental speciation through its developed metrology capability for phosphorus (P) and selenium (Se). Applying these developed principles to effect traceable measurement capability for vanadium compounds, for future application to clinical trial scenarios is timely.

Vanadium drugs (e.g. the organic compound bis-maltolato oxovanadium-BMVO) have potential medicinal use in the treatment of diabetes mellitus - a disease that affects >2m people in the UK alone, at a cost of ~5% of NHS expenditure – as, unlike insulin, vanadium compounds are low molecular weight species that are stable in gastric juice and can be administered orally. Binding of vanadium to transferrin in vitro in response to vanadium drugs (e.g. BMVO) has been reported. Despite numerous studies, the mechanism/s by which vanadium mediates its observed metabolic effects in vivo are still not completely understood owing to the difficulty in achieving highly sensitive/selective determination of this element using conventional ICP-MS detection (due to spectral interferences) and potential transformation of the target species during sample handling and species separation associated with organic MS strategies.

Clarification of the biochemical forms and physiological functions of this element in higher organisms will be facilitated greatly by the provision of accurate measurement methods for traceable quantification and identification of ultra-trace levels of vanadium-containing biomolecules in biological materials.

Aims and objectives

To provide traceable measurement for the identification and quantitation of vanadium-containing biomolecules in biological materials (e.g. serum and tissues) to underpin UK industry and diabetes research into novel, safer and more efficient drugs through:

• Development and validation of novel quantitative extraction procedures for small metabolites and macromolecules of vanadium (e.g. V-transferrin) from biological fluids and tissues
• Development of 2D-chromatography (size exclusion followed by capillary reversed phase, capillary electrophoresis (CE) or fast protein liquid chromatography (LC)) coupled to collision cell ICP-MS methodology for the detection/quantification of vanadium species in relevant models
• Development of enhanced detection capabilities for selective species identification using the parallel combination of high resolution separation with ICP-MS and organic MS (MALDI-MS or ESI QTOF-MS)

Project Outputs

• Presentation of a talk entitled: 'Elemental and Molecular MS: The best combination to study the fate of metallodrugs in disease models?' at the Nordic Plasma Conference 2010 held in Norway.