Liquid Chromatographic Separation of Darunavir Enantiomers on Coated and Immobilized Amylose Tris(3, 5‐Dimethylphenylcarbamate) Chiral Stationary Phases

Abstract

Liquid chromatographic separation of darunavir enantiomers on covalently bonded and physically adsorbed polysaccharide chiral stationary phases was studied at different temperatures. The separations were accomplished under normal-phase conditions by using different combinations of hexane, organic modifiers (2-propanol, 1-propanol and ethanol), and diethylamine as mobile phase solvents. The effect of organic modifiers and the column temperature on retention, separation, and resolution was investigated. The observed differences were explained in terms of the coated and immobilized nature of the two columns. Van't Hoff plots (ln k' vs. 1/T, ln α vs. 1/T) and apparent thermodynamic parameters were derived to understand the effect of temperature on separation.

Liquid chromatographic separation and thermodynamic investigation of lorcaserin hydrochloride enantiomers on immobilized amylose–based chiral stationary phase

“…The equilibrium binding constant ( k i ) that measures the binding strength may be based on standard Gibbs free energy change (ΔG): where R is the universal gas constant (8.3144 J/[mol·K]), T is the absolute temperature in Kelvin, k i is the binding constant, and i denotes the corresponding enantiomers. The large energy difference is set free upon solute and CSP association; because of favorable energetic state of bound versus free solute, this will give large association constant …”

“…The large energy difference is set free upon solute and CSP association; because of favorable energetic state of bound versus free solute, this will give large association constant. [18][19][20] The Gibbs free energy is composed of enthalpic and entropic contributions (ΔH°and ΔS°), the enantiomeric strong binding driven by intermolecular interaction as measured by the enthalpy change ΔH. The process of complexation is usually paid off by an entropic cost ΔS, shown as following Gibbs-Helmholtz equation:…”

Enantioseparation of isoxazolines with functionalized perphenylcarbamate cyclodextrin clicked chiral stationary phases in HPLC

“…The enantioseparations in binary eluents were evaluated by adding different type of organic modifiers since the polarity of mobile phase is a vital factor for NP‐HPLC . As a consequence of adsorption, the incorporation of alcohol modifiers of different steric size/shape may result in different chiral discrimination environments, leading to the change of chiral recognition mechanism . In this study, two alcohols (IPA or EtOH) were used to modulate the enantioseparations.…”

Liquid chromatographic separation and thermodynamic investigation of stereoisomers of darunavir on Chiralpak AD‐Hcolumn

“…Among the four stereoisomers, V is an enantiomer of DRV (I). In an earlier study, the separation of DRV (I) and its enantiomer (V) was investigated on Chiralpak IA and AD‐H columns . In order to extend the study to stereoisomers II, III, and IV, the separation was initially tried on Chiralpak IA, IC, and AD‐H columns under normal‐phase conditions.…”

“…Dailly and colleagues reported a column‐switching LC/MS/MS method for determination of the plasma concentration of DRV along with other ten antiretroviral agents . Previously, the authors’ compared separation of darunavir and its enantiomer (V) on two different viz., Chiralpak AD‐H and Chiralpak IA columns containing stationary phases (i) coated and (ii) immobilized with amylose tris(3,5‐dimethylphenylcarbamate), respectively . However, to the best of authors’ knowledge, there are no reports on separation of DRV from its stereoisomers till today.…”