Study of metabolic pathways of racemic ketamine and its (S)-enantiomer in rat blood plasma using CE-ESI/MS with partial filling of dual chiral selector system

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00619154" target="_blank" >RIV/61388963:_____/25:00619154 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/25:43928372

Výsledek na webu

<a href="https://doi.org/10.1016/j.talanta.2025.128129" target="_blank" >https://doi.org/10.1016/j.talanta.2025.128129</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.talanta.2025.128129" target="_blank" >10.1016/j.talanta.2025.128129</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Study of metabolic pathways of racemic ketamine and its (S)-enantiomer in rat blood plasma using CE-ESI/MS with partial filling of dual chiral selector system

Popis výsledku v původním jazyce

Ketamine is a chiral drug used as anesthetic, analgesic and antidepressant. Its enantiomers and stereoisomers of its metabolites show different pharmacological and behavioral effects. To study the ketamine metabolic pathway and investigate these effects, highly sensitive and enantioselective methods are required. For that reason, in this study, a new CE method using a partial filling dual chiral selector system and ESI-MS detection has been developed and applied for separation and quantification of enantiomers of ketamine and its main metabolites, norketamine, hydroxynorketamine and dehydronorketamine, extracted by dichloromethane from the blood plasma of laboratory rats. The dual chiral selector system consisting of two zones of highly sulfated β-cyclodextrin (30 mg mL−1) and highly sulfated γ-cyclodextrin (10 mg mL−1) was introduced consecutively near the capillary outlet end. Both chiral selectors were dissolved in the background electrolyte composed of 10 mM ammonium hydroxide, 104 mM acetic acid, 10 % (v/v) ethanol, pH∗ 3.75. This system enabled enantioseparation of ketamine and its metabolites within a single CE run. High resolutions (3.99–17.61) of enantiomers of all above four analytes within a short time (11 min) were achieved in the fused silica capillary covalently coated with weakly negatively charged polyanionic copolymer (poly(acrylamide-co-sodium-2-acrylamido-2-methylpropanesulfonate), PAMAMPS). This coating minimized analyte sorption to the capillary and provided good repeatability of migration times. The limits of detection and quantification of the above analytes were in the range 108–238 nM and 361–792 nM, respectively. The method was linear within wide concentration range of 0.1–200 μM and the recovery was 91.3–105 %.

Název v anglickém jazyce

Study of metabolic pathways of racemic ketamine and its (S)-enantiomer in rat blood plasma using CE-ESI/MS with partial filling of dual chiral selector system

Popis výsledku anglicky

Ketamine is a chiral drug used as anesthetic, analgesic and antidepressant. Its enantiomers and stereoisomers of its metabolites show different pharmacological and behavioral effects. To study the ketamine metabolic pathway and investigate these effects, highly sensitive and enantioselective methods are required. For that reason, in this study, a new CE method using a partial filling dual chiral selector system and ESI-MS detection has been developed and applied for separation and quantification of enantiomers of ketamine and its main metabolites, norketamine, hydroxynorketamine and dehydronorketamine, extracted by dichloromethane from the blood plasma of laboratory rats. The dual chiral selector system consisting of two zones of highly sulfated β-cyclodextrin (30 mg mL−1) and highly sulfated γ-cyclodextrin (10 mg mL−1) was introduced consecutively near the capillary outlet end. Both chiral selectors were dissolved in the background electrolyte composed of 10 mM ammonium hydroxide, 104 mM acetic acid, 10 % (v/v) ethanol, pH∗ 3.75. This system enabled enantioseparation of ketamine and its metabolites within a single CE run. High resolutions (3.99–17.61) of enantiomers of all above four analytes within a short time (11 min) were achieved in the fused silica capillary covalently coated with weakly negatively charged polyanionic copolymer (poly(acrylamide-co-sodium-2-acrylamido-2-methylpropanesulfonate), PAMAMPS). This coating minimized analyte sorption to the capillary and provided good repeatability of migration times. The limits of detection and quantification of the above analytes were in the range 108–238 nM and 361–792 nM, respectively. The method was linear within wide concentration range of 0.1–200 μM and the recovery was 91.3–105 %.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

<a href="/cs/project/GA22-22398S" target="_blank" >GA22-22398S: Mikrofluidní a elektronická zařízení pro on-line elektroforetickou analýzu tukové tkáně</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Talanta

ISSN

0039-9140

e-ISSN

1873-3573

Svazek periodika

293

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

128129

Kód UT WoS článku

001471776100001

EID výsledku v databázi Scopus

2-s2.0-105002411678