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

Journal of Clinical Pharmacology
T R BrowneD Wagner

Abstract

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.

References

Jun 15, 1992·Analytical Chemistry·A L BurlingameD H Russell
Sep 1, 1985·Biomedical Mass Spectrometry·A NakagawaI R Kaplan
Oct 1, 1988·Biomedical & Environmental Mass Spectrometry·T Preston, D C McMillan

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Citations

Apr 29, 1998·Journal of Clinical Pharmacology·T R Browne
Sep 14, 2007·Mass Spectrometry Reviews·Jean-Philippe GodinGérard Hopfgartner
Jan 1, 2001·Journal of Liposome Research·F J Belas, I A Blair
Mar 18, 2021·Acta Physiologica·Marie KleinHeimo Mairbäurl
Apr 2, 2021·Frontiers in Physiology·Perumal ThiagarajanJosef T Prchal
Aug 15, 2021·Journal of Pharmaceutical and Biomedical Analysis·Mario ThevisAndreas Thomas

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