Enantioseparation of Mirabegron Using Cyclodextrin‐based Chiral Columns: High‐performance Liquid Chromatography and Molecular Modeling Study DOI Creative Commons

Ali Mhammad,

Gergely Dombi,

Máté Dobó

и другие.

Journal of Separation Science, Год журнала: 2025, Номер 48(4)

Опубликована: Апрель 1, 2025

ABSTRACT A novel high‐performance liquid chromatography method for the enantioseparation of mirabegron ( R ‐mirabegron), a selective β‐3 adrenergic receptor agonist, using cyclodextrin (CD)‐based chiral stationary phases (CSPs) was developed. Seven different CSPs containing β‐, γ‐, hydroxypropyl‐β‐, sulfobutyl‐β‐, carboxymethyl‐β‐, permethyl‐β‐, and phenylcarbamate‐β‐cyclodextrin were evaluated under both polar organic reversed‐phase conditions. Only Chiral CD‐Ph column displayed enantiorecognition. Optimization conditions full factorial design led to determination most suitable conditions: mobile phase composition 90:10:0.1 methanol:water:diethylamine, flow rate 0.8 mL/min, temperature 40°C with enantiomeric elution order, where impurity S ‐mirabegron elutes first. Using optimized conditions, s = 1.9 achieved within 10 min. The developed validated according current guidelines successfully applied ‐mirabegron, as in pharmaceutical formulations. enantiorecognition mechanism investigated by molecular docking thermodynamic analysis. modeling, interactions between CDs analyte analyzed at level, revealing that interacts primarily phenylcarbamate groups on outer surface structure. Enthalpy‐controlled consistently observed across all eluent compositions, regardless is highly routine purity mirabegron, offering reliable tool regulatory compliance.

Язык: Английский

Enantioseparation of Mirabegron Using Cyclodextrin‐based Chiral Columns: High‐performance Liquid Chromatography and Molecular Modeling Study DOI Creative Commons

Ali Mhammad,

Gergely Dombi,

Máté Dobó

и другие.

Journal of Separation Science, Год журнала: 2025, Номер 48(4)

Опубликована: Апрель 1, 2025

ABSTRACT A novel high‐performance liquid chromatography method for the enantioseparation of mirabegron ( R ‐mirabegron), a selective β‐3 adrenergic receptor agonist, using cyclodextrin (CD)‐based chiral stationary phases (CSPs) was developed. Seven different CSPs containing β‐, γ‐, hydroxypropyl‐β‐, sulfobutyl‐β‐, carboxymethyl‐β‐, permethyl‐β‐, and phenylcarbamate‐β‐cyclodextrin were evaluated under both polar organic reversed‐phase conditions. Only Chiral CD‐Ph column displayed enantiorecognition. Optimization conditions full factorial design led to determination most suitable conditions: mobile phase composition 90:10:0.1 methanol:water:diethylamine, flow rate 0.8 mL/min, temperature 40°C with enantiomeric elution order, where impurity S ‐mirabegron elutes first. Using optimized conditions, s = 1.9 achieved within 10 min. The developed validated according current guidelines successfully applied ‐mirabegron, as in pharmaceutical formulations. enantiorecognition mechanism investigated by molecular docking thermodynamic analysis. modeling, interactions between CDs analyte analyzed at level, revealing that interacts primarily phenylcarbamate groups on outer surface structure. Enthalpy‐controlled consistently observed across all eluent compositions, regardless is highly routine purity mirabegron, offering reliable tool regulatory compliance.

Язык: Английский

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