USE OF STABLE ISOTOPES PHARMACOLOGY

Stable isotope labels are used in tracer studies, to follow the pathway of a drug, or else, but equally important, to distinguish between a true drug metabolite and a naturally occurring substance in a biological sample. But probably the most widespread use to date has been as an internal standard for quantitative gas chromatography-mass spectrometry. Addition of a stable isotope labelled drug or metabolite in known amount to a mixture enables a quantitative assessment of the natural compound to be made from the mass spectral data. 

Metabolic switching has been reported as a consequence of deuterium labelling where a drug is metabolised by multiple alternate pathways rather than sequentially [20,21]. Both in vivo studies in rats and in vitro studies using rat 

As the cost differentia] narrows, especially of synthesized compounds, and taking the other factors mentioned above into consideration, it seems likely that carbon-13 and/or nitrogen-1 S labelling will become the preferable choice where practicable in future metabolic studies. 

Many of the disadvantages of stable isotope labelling as compared with radiolabelling stem from limits on the sensitivity which arise from the natural abundance background. Using multiple labelled compounds as tracers, this problem can be overcome and furthermore, an assessment may be made of isotope effects in the system under study. The use of multiple labelled compounds and methods of detection allowing the determination of 1 pg in a 1 pg sample have been reviewed [65]. 

---