A parallel chiral–achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome

Abstract

A parallel chiral/achiral LC-MS/MS assay has been developed and validated to measure the plasma and urine concentrations of the enantiomers of ketamine, (R)-and (S)-Ket, in Complex Regional Pain Syndrome (CRPS) patients receiving a 5-day continuous infusion of a subanesthetic dose of (R,S)-Ket. The method was also validated for the determination of the enantiomers of the Ket metabolites norketamine, (R)-and (S)-norKet and dehydronorketamine, (R)-and (S)-DHNK, as well as the diastereomeric metabolites hydroxynorketamine, (2S,6S)-/(2R, 6R)-HNK and two hydroxyketamines, (2S,6S)-HKet and (2S,6R)-Hket. In this method, (R,S)-Ket, (R,S)-norKet and (R,S)-DHNK and the diastereomeric hydroxyl-metabolites were separated and quantified using a C 18 stationary phase and the relative enantiomeric concentrations of (R,S)-Ket, (R,S)-norKet and (R,S)-DHNK were determined using an AGP-CSP. The analysis of the results of microsomal incubations of (R)-and (S)-Ket and a plasma and urine sample from a CRPS patient indicated the presence of 10 additional compounds and glucuronides. The data from the analysis of the patient sample also demonstrated that a series of HNK metabolites were the primary metabolites in plasma and (R)-and (S)-DHNK were the major metabolites found in urine. The results suggest that norKet is the initial, but not the primary, metabolite and that downstream norKet metabolites play a role in (R,S)-Ket-related pain relief in CRPS patients.

The distribution and clearance of (2S,6S)‐hydroxynorketamine, an active ketamine metabolite, in Wistar rats

“…2010). The achiral portion of the analytical method was cross-validated for use in this study using plasma (Bioreclamation, East Meadow, NY) and whole brains (SRI International) obtained from drug-free Wistar rats.…”

“…2009; Moaddel et al. 2010; Zarate et al. 2012) and in studies utilizing human microsomal preparations (Desta et al.…”

Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters

“…at a dose of 0.5 mg/kg. For the binding and functional studies, (S)-ketamine, (R)-ketamine, (S)-norketamine, (R)-norketamine, (S)-DHNK, (R)-DHNK, (2S,6S)-HNK, (2R,6R)-HNK, (2R,6S)-HNK, and (2S,6R)-HNK were synthesized as previously described (Moaddel et al, 2010;Zanos et al, 2016).…”

Electroanalytical Sensing of Ketamine Using Electrogenerated Chemiluminescence

“…3,5 In fact, ketamine has surpassed other club drugs and even replaced heroin as the predominant drug of abuse in Hong Kong since the early 2000 7 with user experiencing hallucinations and a cataleptic state called the "K-hole." 5,6 Ketamine is generally analyzed by using immunoassays, 8 Liquid Chromatography-Mass Spectroscopy (LC-MS) 2,9,10 or Gas Chromatography-Mass Spectroscopy (GC-MS) [11][12][13] methodologies in biological matrixes. The drawbacks to these methods are that the times for the analysis are longer than 6 minutes per sample and a liquidliquid extraction prior to analysis is also needed.…”