GC-MS and /sup 17/O NMR tracer studies of Et/sub 3/PO formation from auranofin and H/sub 2//sup 17/O in the presence of bovine serum albumin: an in vitro model for auranofin metabolism

Journal Article · Wed Sep 21 00:00:00 EDT 1988 · Inorg. Chem.; (United States)

DOI:https://doi.org/10.1021/ic00292a027· OSTI ID:6277262

Isab, A A; Shaw, III, C F; Locke, J

/sup 17/O NMR spectroscopy and gas chromatographic-mass spectral analysis have been used to monitor the source of oxygen in the triethylphosphine oxide formed by the reaction of the antiarthritic drug auranofin ((2,3,4,6-tetra-O-acetyl-..beta..-D-1-glucopyranosato)(triethylphosphine)gold(I)) and bovine serum albumin (BSA) in the presence of reduced glutathione (GtSH). A procedure to extract Et/sub 3/PO from aqueous solutions and concentrate it for subsequent analyses was developed. When the in vitro reaction is carried out aerobically in /sup 17/O-enriched water, Et/sub 3/P/sup 17/O is generated. The chemical ionization (CH/sub 4/) mass measurement, (m + 1)/z = 135, and the /sup 17/O NMR parameters (delta/sub O/ = 40.6 and /sup 1/J/sub PO/ = 156 /plus minus/ 5 Hz) unambiguously establish its identity. The SH titer of the albumin (mole ratio of protein SH groups to BSA) increases during the reaction, confirming that albumin disulfide bonds are reduced in the reaction. Under aerobic conditions, the enriched Et/sub 3/PO accounts for at least 60% of the Et/sub 3/PO formed. The significance of these results for the in vivo formation of Et/sub 3/PO, an auranofin metabolite, is discussed. 25 references, 2 figures.

• Research Organization: Univ. of Wisconsin, Milwaukee (USA)
• OSTI ID: 6277262
• Journal Information: Inorg. Chem.; (United States), Vol. 27:19
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
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MASS SPECTROSCOPY
NMR SPECTRA
OXYGEN 17
ANIMALS
CHROMATOGRAPHY
DATA
DOMESTIC ANIMALS
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550604* - Medicine- Unsealed Radionuclides in Therapy- (1980-)