(13)C/(15)N-Enriched l-Dopa as a Triple-Resonance NMR Probe to Monitor Neurotransmitter Dopamine in the Brain and Liver Extracts of Mice.

In an attempt to monitor μm-level trace constituents, we applied here (1)H-{(13)C-(15)N} triple-resonance nuclear magnetic resonance (NMR) to (13)C/(15)N-enriched l-Dopa as the inevitable precursor of the neurotransmitter dopamine in the brain. The perfect selectivity (to render endogenous components silent) and μm-level sensitivity (700 MHz spectrometer equipped with a cryogenic probe) of triple-resonance allowed the unambiguous and quantitative metabolic and pharmacokinetic analyses of administered l-Dopa/dopamine in the brain and liver of mice. The level of dopamine generated in the brain (within the range 7-76 μm, which covers the typical stimulated level of ∼30 μm) could be clearly monitored ex vivo, but was slightly short of the detection limit of a 7 T MR machine for small animals. This work suggests that μm-level trace constituents are potential targets of ex vivo monitoring as long as they contain N atom(s) and their appropriate (13)C/(15)N-enrichment is synthetically accessible.