Funds are requested for the purchase of a Thermo Finnigan TSQ Quantum triple quadrupole mass spectrometer and an accompanying Thermo Finnigan Surveyor liquid chromatography system. This instrumentation would become part of the University of Minnesota Cancer Center's Analytical Biochemistry Core facility where the quantitative analyses of carcinogen metabolites and DNA adducts outline in this proposal are performed. Triple quadrupole mass spectrometry is the ideal approach for quantitative analyses, as it presents the best combination of specificity, sensitivity, and quantitative precision. The recently released TSQ Quantum instrument represents a leap forward in sensitivity and resolution over Thermo Finnigan's previous state-of-the-art triple quadrupole instrument, the TSQ 7000. The Core facility currently operates a TSQ 7000 to perform all the gas chromatography and liquid chromatography quantitative analyses done in the facility. The TSQ Quantum has demonstrated a sensitivity improvement of a factor of at least 15 over the TSQ 7000 for reserpine, a commonly used compound for comparisons of atmospheric pressure ionization sensitivity (API). It has been designed to operate at 0.1 amu resolution (full width at half maximum peak height, FWHM) resolution as compared to 0.7 amu FWHM resolutions for the TSQ 7000. The additional selectivity afforded by high resolution precursor selection and/or high resolution neutral loss operation will eliminate much of the chemical noise associated with complex biological matrices still present in MS/MS data collected at nominal mass resolution. The improved sensitivity and resolution will allow for the measurement of trace compounds at attomole to femtomole levels in samples derived from complex matrices such as urine and blood. Four principal investigators at the University of Minnesota Cancer Center are in need of the low limits of detection and quantitative precision the TSQ Quantum provides. A central theme encompassing the research of these investigators is the elucidation of the mechanisms by which people develop cancer from tobacco smoke exposure. The researchers attack the problem from complementary directions and make up a critical mass for understanding what is one of the most direct links between common environmental exposure and cancer. ? ?
