The objective of this project is development of new mass spectral techniques in order to provide innovative and/or more rapid solutions to problems involving (1) chemical structure determination, (2) complex mixture analysis and (3) measurement of trace components in biological systems. Electrospray ionization mass spectrometry (ESI/MS), tandem mass spectrometry (MS/MS) and combined liquid chromatography-mass spectrometry (LC/MS) are the techniques of current interest. A narrow- bore (2 mm i.d., 0.200 ml/min), reversed-phase liquid chromatography system, whose flow can be automatically diverted for sample desalting, has been employed to develop a rapid method utilizing tandem mass spectrometry for measuring the Phase I anti-AIDS drug 2'-b-fluoro-2',3'- dideoxyadenosine (F-ddA) and its anti-HIV-active deaminated metabolite 2'-b-fluoro-2',3'-dideoxyinosine (F-ddI) in human plasma with high specificity and sensitivity. This methodology is being applied to determine the pharmacokinetics and bioavailability of oral F-ddA during the initial Phase I clinical trial of this agent in AIDS patients. Fast atom bombardment mass spectrometry (FAB/MS) is used to support the LMCH synthetic effort through structural characterization of new compounds and synthetic intermediates. FAB liquid matrix reactions involving ion pairing, reduction, dehalogenation and radical cation/anion formation continue to be studied and characterized to ensure the interpretability and reliability of these analyses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC006178-13
Application #
6100889
Study Section
Special Emphasis Panel (LMC)
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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