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Stable isotope-mass spectrometry in drug metabolism and pharmacokinetics

Conference ·
OSTI ID:4419244

From first international conference on stable isotopes in chemistry, biology, and medicine; Argonne, lllinois, USA (9 May 1973). In proceedings of the first international conference on stable isotopes in chemistry, biology, and medicine. The 3-hydroxylation of diazepam to yield 3-hydroxy-diazepam was investigated in an attempt to study the NADPH-dependent oxygenation of nitrogen containing compounds. The source of oxygen was identified by high and low resolution mass spectrometry as molecular oxygen using separate microsomal incubations with /sup 18/O enriched H/sub 2/O and O/sub 2/. The /sup 18/O enriched acetic an hydride induced rearrangement of acetoxydiazepam to diazepara N-4-oxide was studied as a chemical model for the possible role of the Noxide as enzymatic intermediate, which undergoes N to C oxygen migration. The retained N- oxide /sup 16/O could be located in acetoxydiazepam by analyzing the parent ion and kev fragments. In a separate study, human plasma and urine levels of diazoxide were measured in four patients by stable isotope dilution-GC-mass fragmentography. d3-Diazoxide served as internal standard. Conditions were developed to prevent the exchange of the label during derivatization for GC and on column. Sensitivity by repetitive scanning over the parent ions was 1 ng diazoxide/sample. (ERB)

Research Organization:
Univ. of Southern California, Los Angeles; Argonne National Lab., Ill. (USA)
NSA Number:
NSA-29-000847
OSTI ID:
4419244
Report Number(s):
CONF-730525--
Country of Publication:
Country unknown/Code not available
Language:
English