Online Enantioselective Capillary Electrophoretic Method for Screening Cytochrome P450 3A4 Inhibitors

Řemínek, Roman; Glatz, Zdeněk; Thormann, Wolfgang

doi:10.1007/978-1-0716-0163-1_11

Cited by 2 publications

(3 citation statements)

References 21 publications

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“…The same group in close cooperation with Prof. Thormann, and under his guidance, subsequently applied this multi-plug TDLFP modification to a study of enantioselective drug metabolism by CYP enzymes, more specifically to the CYP3A4-mediated N-demethylation pathway of ketamine [40,41], a drug used as an anesthetic and as a treatment for depression and pain management [42]. The chiral separation of racemic drugs is a necessary step in the pharmaceutical industry as well as in clinical therapy.…”

Section: Drug Metabolism Studiesmentioning

confidence: 99%

Atypical applications of transverse diffusion of laminar flow profiles methodology for in‐capillary reactions in capillary electrophoresis

Bržezická,

Kohútová,

Glatz

2024

J of Separation Science

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Capillary electrophoresis (CE) is a powerful separation technique offering quick and efficient analyses in various fields of bioanalytical chemistry. It is characterized by many well‐known advantages, but one, which is perhaps the most important for this application field, is somewhat overlooked. It is the possibility to perform chemical and biochemical reactions at the nL scale inside the separation capillary. There are two basic formats applicable for this purpose, heterogeneous and homogeneous. In the former, one reactant is immobilized onto a particle or monolithic support or directly on the capillary wall, and the other is injected. In the latter, the reactant mixing inside a capillary is based on electromigration or diffusion. One of the diffusion‐based methodologies, termed Transverse Diffusion of Laminar Flow Profiles, is the subject of this review. Since most studies utilizing in‐capillary reactions in CE focus on enzymes, which are being continuously and exhaustively reviewed, this review covers the atypical applications of this methodology, but still in the bioanalytical field. As can be seen from the demonstrated applications, they are not limited to reactions, but can also be utilized for other biochemical systems.

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Section: Drug Metabolism Studiesmentioning

confidence: 99%

Atypical applications of transverse diffusion of laminar flow profiles methodology for in‐capillary reactions in capillary electrophoresis

Bržezická,

Kohútová,

Glatz

2024

J of Separation Science

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“…Execution of an enzymatic reaction performed in a capillary with subsequent electrophoretic analysis of the formed products referred to as EMMA was successfully adapted to reactions with chiral drug substrates together with chiral separations and analysis of the formed products. This format with highly sulfated CDs as chiral selectors was used to study the demethylation of ketamine to norketamine catalyzed by human CYP3A4 [61,77,100], of fluoxetine to norfluoxetine in presence of CYP2D6 [74] and of verapamil to norverapamil mediated by CYP3A4 [75]. In all three cases, metabolite formation rates were fitted to the Michaelis-Menten model and or the Hill equation followed by the elucidation of the characteristic V max and K values for the product enantiomers.…”

Section: Assessment Of Drug Metabolism and Inhibition In Vitromentioning

confidence: 99%

“…Thus, such an online system can be used for the fast assessment of enzymatic metabolic steps as well as for screening of putative reaction inhibitors. A detailed protocol is given in [100]. This example illustrates that CE is a promising technique for enantioselective drug metabolism studies due to highly effective separations, minuscule consumption of sample and reagents, and high throughput via automation.…”

Section: Applicationsmentioning

confidence: 99%

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

Caslavska

Thormann

2021

Electrophoresis

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The further development and application of capillary electromigration techniques for the enantioselective determination of drugs and their metabolites in body fluids, tissues, and in vitro preparations during the 2010 to 2020 time period continued to proof their usefulness and attractiveness in bioanalysis. This review discusses the principles and important aspects of capillary electrophoresis‐ based chiral drug bioassays, provides a survey of the assays reported during the past 10 years and presents an overview of the key achievements encountered in that time period. For systems with charged chiral selectors, special attention is paid on assays that feature field‐amplified sample injection to enable the determination of ppb levels of analytes and optimized online incubation procedures for the rapid assessment of a metabolic pathway. Applications discussed encompass the pharmacokinetics of drug enantiomers in vivo and in vitro, the impact of inhibitors on metabolic steps, the elucidation of the stereoselectivity of drug metabolism in vivo and in vitro, and drug enantiomers in toxicological, forensic, and doping analysis.

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Online Enantioselective Capillary Electrophoretic Method for Screening Cytochrome P450 3A4 Inhibitors

Cited by 2 publications

References 21 publications

Atypical applications of transverse diffusion of laminar flow profiles methodology for in‐capillary reactions in capillary electrophoresis

Atypical applications of transverse diffusion of laminar flow profiles methodology for in‐capillary reactions in capillary electrophoresis

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

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