Performance of Human Mass Balance/Metabolite Identification Studies Using Stable Isotope (13C,15N) Labeling and Continuous-Flow Isotope-Ratio Mass Spectrometry as an Alternative to Radioactive Labeling Methods

Autor: George K. Szabo, Thomas R. Browne, David A. Wagner, Alfred Ajami
Rok vydání: 1993
Předmět:
Zdroj: The Journal of Clinical Pharmacology. 33:246-252
ISSN: 0091-2700
DOI: 10.1002/j.1552-4604.1993.tb03951.x
Popis: Stable isotope labeling in therapeutic and subtherapeutic quantities of drug (15N2(13)C-phenobarbital) can be quantitated in biological matrices (urine) and high performance liquid chromatography (HPLC) peaks from urine using continuous-flow isotope-ratio mass spectrometry (CF-IRMS). Standard curves for 15N2(13)C-phenobarbital were reproducible and linear (R2 > 0.985) over the ranges of 3-100 micrograms/ml for whole urine (15N2 or 13C labeling) and 0.1-8.0 micrograms/mL for HPLC peaks derived from urine (15N2 labeling). The lower limit of quantitation values for urine drug concentration was 0.46-2.62 micrograms/mL in whole urine and 0.10-0.70 micrograms/mL in HPLC peaks. Validation samples quantitated with these standard curves yielded close to expected values. These data suggest stable isotope labeling and CF-IRMS may be used as an alternative to 14C labeling and radioactivity counting methods in mass balance/metabolite identification and other biomedical studies.
Databáze: OpenAIRE