13C/15N‐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 1H-{13C-15N} triple-resonance nuclear magnetic resonance (NMR) to 13C/15N-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 7T 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 13C/15N-enrichment is synthetically accessible.

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