Chiral LC-MS/MS method for the simultaneous determination of (R,S)-ketamine, (R,S)-norketamine, and (2R,6R;2S,6S)-hydroxynorketamine in mouse plasma and brain.
J Pharm Biomed Anal
; 224: 115168, 2023 Feb 05.
Article
em En
| MEDLINE
| ID: mdl-36473323
ABSTRACT
A convenient LC-MS/MS assay method to simultaneously and sensitively determine (R,S)-ketamine (Ket), (R,S)-norketamine (NK), and (2R,6R;2S,6S)-hydroxynorketamine (HNK) enantiomers in plasma and brain from mice was developed. This method enables the chiral separations of these six enantiomers in one analysis by constructing a column-switching system composed of one achiral column and two chiral columns with a relatively short analysis time (17 min). The chromatography involves the separation of (2R,6R;2S,6S)-HNK from (R,S)-Ket and (R,S)-NK on an octadecyl-silica column, followed by chiral separations on a CHIRALPAK AY-RH column for (2R,6R;2S,6S)-HNK or on a CHIRALPAK AS-RH column for the other analytes. The calibration curves for plasma and brain showed a good linearity in the range of 3-1000 ng/mL and 1.5-500 ng/g, respectively. The accuracy ranged from 90.0% to 104.0% in within-run and between-run. This validated method was applicable to determine the stereoselective pharmacokinetic profiles of (R,S)-Ket, (R,S)-NK, and (2R,6R;2S,6S)-HNK in plasma and brain collected from individual mice after a single intraperitoneal dosing of racemic Ket at an antidepressant dose. It is hoped that this assay will greatly help for understanding the relationship between the antidepressant actions of (R,S)-Ket enantiomers or their metabolites and their pharmacokinetics.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ketamina
Limite:
Animals
Idioma:
En
Revista:
J Pharm Biomed Anal
Ano de publicação:
2023
Tipo de documento:
Article