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Synthesis of carbon-14 labeled ketamine and norketamine
Lu Chen1, Yong Gong1, Rhys Salter1
1Isotope Chemistry and Biotransformations, Janssen Research & Development, Johnson & Johnson, Spring House, Pennsylvania.
Abstract:
Ketamine is a well-known general anesthetic that inhibits cerebral NMDA receptors. Norketamine is a major circulating metabolite of this drug. A nasal spray formulation of esketamine, the S enantiomer of ketamine, is under development for the management of treatment-resistant depression. To assess the pharmacokinetic properties, C-14 labeled ketamine and norketamine were prepared separately from commercially available [14 C]CuCN through a five-step sequence with the C-14 label at the quaternary carbon of the cyclohexyl ring. Chiral resolution of [14 C]ketamine and chiral column separation of [14 C]norketamine resolved/separated the (S)-enantiomers from (R)-enantiomers.
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