Enantioseparation of racemic paroxol on an amylose‐based chiral stationary phase by supercritical fluid chromatography

Abstract

The separation of racemic paroxol, a key precursor of trans-(-)-paroxetine, on Chiralpak AD-H, an amylose-based chiral stationary phase, by supercritical fluid chromatography was studied. Pulse experiments were investigated using supercritical carbon dioxide modified with methanol (MeOH), ethanol and 2-propanol at 35°C and 15 MPa. Retention and separation factors were determined under analytical conditions for different mobile phase compositions. Among the modifiers used, MeOH was shown to be the best additive, and 5% v/v of MeOH was the preferable concentration at which selectivity of 1.14 and resolution of 3.0 was obtained. In order to evaluate the potential with respect to preparative separations, the adsorption isotherms of individual enantiomers of paroxol were estimated using the elution by characteristic point method. Isotherm parameters were determined from the overloaded elution profiles that were collected at pressure ranging from 15 to 24 MPa. The isotherms obtained were further validated by comparing experimentally recorded elution profiles with the predictions based on the equilibrium-dispersive model. The results are important to the process design and optimization of preparative supercritical fluid chromatography application.

Determination of adsorption isotherms in supercritical fluid chromatography

“…(12) where the ideal model's simulated front retention times were calculated using the algorithm in [33]. The estimated adsorption isotherm parameters are presented in Table 2 and plotted in Fig.…”

“…In SFC, only a handful papers deals with the determination of adsorption isotherms [1] and in even fewer cases the estimated adsorption isotherms are verified by comparing simulated and experimental overloaded elution profiles [10][11][12]. We suspect three reasons for this: (i) the lack of fundamental SFC understanding, (ii) the lack of commercial SFC systems properly evaluated for fundamental studies and (iii) the previous relatively low interest in the SFC area.…”

“…The density variation never exceeded 1.63%. • Bao et al [12] used ECP to determine the Langmuir adsorption isotherms of paroxol enantiomers on a Chiralpak AD-H column with different alcohols as modifiers. Although investigating the effect of pressure, no detailed discussion of possible variations in volumetric flow rate due to density gradients was given.…”