A Reversed-Phase Mode LC-MS/MS Method Using a Polysaccharide Chiral Selector for Simultaneous Quantitation of Each Enantiomer of Tramadol and its Metabolites in Human Plasma and Evaluation of CYP-Mediated Stereoselective Demethylation.
Ther Drug Monit
; 42(3): 503-511, 2020 06.
Article
en En
| MEDLINE
| ID: mdl-31613803
ABSTRACT
BACKGROUND:
The enantiomeric pharmacokinetics and metabolism of tramadol and its metabolites have not fully been understood. This study aimed to develop a reversed-phase mode liquid chromatography coupled to a tandem mass spectrometry method for the enantiomeric quantitation of tramadol and its metabolites in human plasma and to evaluate the stereoselective demethylation.METHODS:
Racemic tramadol and its metabolites in plasma specimens were separated using a chiral selector coated with cellulose tris(3,5-dimethylphenylcarbamate) on silica gel under a reversed-phase mode. The mass spectrometer ran in the positive ion multiple-reaction monitoring mode. This method was performed to quantify plasma samples from 20 cancer patients treated with oral tramadol. The stereoselective demethylation was evaluated using recombinant cytochrome P450 (CYP) enzymes.RESULTS:
The calibration curves of (+)- and (-)-tramadol, (+)- and (-)-O-desmethyltramadol (ODT), and (+)- and (-)-N-desmethyltramadol (NDT) were linear over the plasma concentration ranges of 6.25-800, 1.25-160, and 3.13-400 ng/mL for the respective enantiomers. In the present method, the intra- and inter-day accuracies and imprecisions were 94.2%-108.3% and 0.5%-6.0% for all analytes. The plasma concentrations of (+)-tramadol and NDT were higher than those of (-)-enantiomers. In contrast, no differences were observed between the plasma concentrations of (+)- and (-)-ODT. In the demethylation assay, the O-demethylations of tramadol and NDT by CYP2D6 were (-)-form-selective.CONCLUSIONS:
The present method can be useful in the enantiomeric evaluation of tramadol and its metabolites in human plasma. Although CYP2D6 contributed to the stereoselective demethylation of tramadol, remarkable differences between (+)- and (-)-ODT were not observed in the plasma of the cancer patients.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tramadol
/
Cromatografía Liquida
/
Sistema Enzimático del Citocromo P-450
/
Espectrometría de Masas en Tándem
/
Analgésicos Opioides
Límite:
Humans
Idioma:
En
Revista:
Ther Drug Monit
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón