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Abstract No.: JMS-Awards-4
Speaker: Brendan Prideaux
Session: JMS Awards
Presentation date: Thu, Aug 31, 2006
Presentation time: 13:30 – 15:00

Applications of Imaging Matrix Assisted Laser Desorption Ionisation - Mass Spectrometry to the Study of Dermal Absorption of Isocyanates

Brendan Prideaux1, Malcolm R. Clench1, Vikki A. Carolan1, Jackie Morton2, Bob Rajan-Sithamparanadarajah3

1 Sheffield Hallam University, Sheffield, United Kingdom
2 Health and Safety Laboratory, Buxton, United Kingdom
3 Health and Safety Executive, Bootle, United Kingdom

Correspondence address: Brendan Prideaux, Sheffield Hallam University, Biomedical Research Centre, Howard Street, Sheffield, S1 1WB United Kingdom.

Keywords: Environmental; Imaging; Ionization, Matrix-Assisted Laser Desorption; MALDI.

Novel aspect: Dermal absorption depth profiling of isocyanates, alcohol derivatisation and membrane blotting extraction method.

 

Isocyanates are commonly used in industry in the manufacture of polyurethane products such as foams, paints and plastics. They are highly reactive compounds, known to produce adverse effects in humans after exposure. Dermal exposure is of particular concern although the mechanisms of this are poorly understood. In the work described here the dermal penetration of isocyanates was investigated using Matrix Assisted Laser Desorption Ionisation - Time of Flight - Mass Spectrometry. We have previously utilised MALDI-TOF-MS to investigate low molecular weight compounds present in skin. Imaging software enables the distribution of the analytes in the skin to be observed, and thus any dermal penetration to be detected

All analyses were conducted using an Applied Biosystems "Q-Star" hybrid quadrupole instrument, fitted with an orthogonal MALDI ion source. 50 µl of a range of isocyanate compounds including hexamethylene diisocyanate (HDI) and toluene diisocyanate (TDI) were pipetted directly onto porcine skin. Isocyanates were applied at a range of concentrations in dimethyl sulfoxide and acetonitrile. Tissue samples were incubated and blotted onto cellulose membranes. Imaging software, supplied by MDS Sciex, was utilised to process the data and provide images of isocyanate distribution on the membrane surfaces. An "on-membrane" alcohol derivatisation process was developed to form a stable urethane derivative to enhance sensitivity.

The distribution of the protonated molecule of an alcohol derivative of each isocyanate was used to generate images of the distribution of the isocyanate on the tissue surface and in vertical skin sections. Preliminary results have shown that it is possible to observe the qualitative penetration of isocyantes through the skin following exposure at various time points.