Application of capillary gas chromatography-reaction interface/mass spectrometry to the selective detection of sup 13 C-, sup 15 N-, sup 2 H-, and sup 14 C-labeled drugs and their metabolites

Thesis/Dissertation · Sun Jan 01 04:00:00 EST 1989

OSTI ID:5735558

Chace, D H

A novel reaction interface/mass spectrometer (RIMS) technique has been applied to the selective detection of {sup 13}C-, {sup 15}N-, {sup 2}H-, and {sup 14}C-labeled phenytoin and its metabolites in urine following separation by capillary gas chromatography. The microwave-powered reaction interface converts materials from their original forms into small molecules whose mass spectra serve to identify and quantify the nuclides. The presence of each element is followed by monitoring the isotopic variants of CO{sub 2}, NO, H{sub 2}, or CH{sub 4} that are produced by the reaction interface. Chromatograms showing only enriched {sup 13}C and {sup 15}N were produced using the net {sup 13}CO{sub 2} or {sup 15}NO signal derived by subtracting the abundance of naturally occurring isotopes from the observed M + 1 signal. When hydrogen was used as a reactant gas, a selective chromatogram of {sup 2}H (D) was obtained by measuring HD at m/Z 3.0219, and a chromatogram showing {sup 14}C was obtained by measuring {sup 14}CH{sub 4} at m/Z 18.034 with a high resolution. For a stable isotope detection, metabolites representing less than 1.5% of the total labeled compounds could be detected in the chromatogram. Detection limits of 170 pCi/mL (34 pCi on column that is equivalent to 187 pg) of a {sup 14}C- labeled metabolite was detected. To identify many of these labeled peaks (metabolites), the chromatographic analysis was repeated with the reaction interface turned off and mass spectra obtained at the retention times found in the RIMS experiment. In addition to the ability of GC-RIMS to detect the presence of {sup 13}C-, {sup 15}N-, and {sup 2}H- (D), it can also quantify the level of enrichment. Enrichment of {sup 13}C and {sup 15}N is quantified by measuring the ratio of excess {sup 13}CO{sub 2} to total {sup 12}CO{sub 2} or excess {sup 15}NO to total {sup 14}NO.

• Research Organization: George Washington Univ., Washington, DC (USA)
• OSTI ID: 5735558
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANTICONVULSANTS
CARBON 13
CARBON 14 COMPOUNDS
CARBON ISOTOPES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL ANALYSIS
CHROMATOGRAPHY
DEUTERIUM
DRUGS
EVEN-ODD NUCLEI
GAS CHROMATOGRAPHY
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPE RATIO
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MASS SPECTROSCOPY
METABOLISM
METABOLITES
NITROGEN 15
NITROGEN ISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
SEPARATION PROCESSES
SPECTROSCOPY
STABLE ISOTOPES
TRACER TECHNIQUES