8 research outputs found
The pharmacokinetics of orally administered S-carboxymethyl-L-cysteine in the dog, calf and sheep
Recombinant heteromeric phenylalanine monooxygenase and the oxygenation of carbon and sulfur substrates
An investigation into possible xenobiotic–endobiotic inter-relationships involving the amino acid analogue drug, S-carboxymethyl-l-cysteine and plasma amino acids in humans
Use of Human Microsomes and Deuterated Substrates: An Alternative Approach for the Identification of Novel Metabolites of Ketamine by Mass Spectrometry
In vitro biosynthesis using pooled human liver microsomes was applied to
help identify in vivo metabolites of ketamine by liquid chromatography
(LC)-tandem mass spectrometry. Microsomal synthesis produced
dehydronorketamine, seven structural isomers of hydroxynorketamine, and at
least five structural isomers of hydroxyketamine. To aid identification,
stable isotopes of the metabolites were also produced from tetra-deuterated
isotopes of ketamine or norketamine as substrates. Five metabolites (three
hydroxynorketamine and two hydroxyketamine isomers) gave chromatographically
resolved components with product ion spectra indicating the presence of a
phenolic group, with phenolic metabolites being further substantiated by
selective liquid-liquid extraction after adjustments to the pH. Two
glucuronide conjugates of hydroxynorketamine were also identified. Analysis by
LC-coupled ion cyclotron resonance mass spectrometry gave unique masses in
accordance with the predicted elemental composition. The metabolites,
including the phenols, were subsequently confirmed to be present in urine of
subjects after oral ketamine administration, as facilitated by the addition of
deuterated metabolites generated from the in vitro biosynthesis. To our
knowledge, phenolic metabolites of ketamine, including an intact glucuronide
conjugate, are here reported for the first time. The use of biologically
synthesized deuterated material as an internal chromatographic and mass
spectrometric marker is a viable approach to aid in the identification of
metabolites. Metabolites that have particular diagnostic value can be selected
as candidates for chemical synthesis of standards