Oxidized sulfur-containing amino acids are recognized as agonists of e
xcitatory amino acid receptors in the mammalian nervous system. Homolo
gues of glutamic acid (homocysteine sulfinic acid and homocysteic acid
) and aspartic acid (cysteine sulfinic acid and cysteic acid) have bee
n shown to be agonistic to N-methyl-D-aspartate receptors in animal br
ain and have been demonstrated in brain tissue. Considerable evidence
exists for the role of homocysteic acid and cysteine sulfinic acid as
endogenous ligands for excitatory amino acid receptors. We report, for
the first time, the quantitation of these compounds in normal human s
erum, by a newly developed gas chromatography-mass spectrometry method
that employs stable isotope-dilution selected ion monitoring using in
ternal standards prepared in our laboratory. We also report new method
s of synthesis of stable isotope-labeled internal standards used in me
asuring cysteine sulfinic acid, cysteic acid, homocysteine sulfinic ac
id, and homocysteic acid. (C) 1994 Academic Press, Inc.