Predictability of Enantiomeric Chromatographic Behavior on Various Chiral Stationary Phases Using Typical Reversed Phase Modeling Software

Abstract

Pharmaceutical companies worldwide tend to apply chiral chromatographic separation techniques in their mass production strategy rather than asymmetric synthesis. The present work aims to investigate the predictability of chromatographic behavior of enantiomers using DryLab HPLC method development software, which is typically used to predict the effect of changing various chromatographic parameters on resolution in the reversed phase mode. Three different types of chiral stationary phases were tested for predictability: macrocyclic antibiotics-based columns (Chirobiotic V and T), polysaccharide-based chiral column (Chiralpak AD-RH), and protein-based chiral column (Ultron ES-OVM). Preliminary basic runs were implemented, then exported to DryLab after peak tracking was accomplished. Prediction of the effect of % organic mobile phase on separation was possible for separations on Chirobiotic V for several probes: racemic propranolol with 97.80% accuracy; mixture of racemates of propranolol and terbutaline sulphate, as well as, racemates of propranolol and salbutamol sulphate with average 90.46% accuracy for the effect of percent organic mobile phase and average 98.39% for the effect of pH; and racemic warfarin with 93.45% accuracy for the effect of percent organic mobile phase and average 99.64% for the effect of pH. It can be concluded that Chirobiotic V reversed phase retention mechanism follows the solvophobic theory.

Comprehensive Review on Chiral Stationary Phases in Single-Column Simultaneous Chiral–Achiral HPLC Separation Methods

“…The teicoplanin and ristocetin A- and amylose tris (3,5-dimethylphenylcarbamate)-based CSPs did not show a specific RP retention behavior, probably due to the importance of the hydrogen bond interactions in their separation mechanism. Interestingly, the vancomycin-based CSP showed a typical RP retention mechanism with good predictability of its enantiomeric selectivity [ 91 , 92 ]. Similarly, the hydroxypropyl-modified β-cyclodextrin CSP showed good predictability in the separation of atropisomers [ 93 ].…”

Enantiomeric Separation of Underivatized Amino Acids: Predictability of Chiral Recognition on Ristocetin A Chiral Stationary Phase

“…DryLab software was successfully used to predict the chiral chromatographic behavior of several compounds on Chirobiotic V, which is expected to dramatically ease method development of enantiomer separations of some racemic drugs on this CSP. 18 This also led to a better understanding of the chiral recognition of the CSPs regarding the studied analyte and parameters. 18 Investigating the predictability of enantioseparation of underivatized amino acids on ristocetin A chiral stationary phase using the DryLab software will provide more information regarding the chiral recognition mechanisms involved in the enantioseparation of the amino acids used in this study.…”

“…DryLab software was successfully used to predict the chiral chromatographic behavior of several compounds on Chirobiotic V, which is expected to dramatically ease method development of enantiomer separations of some racemic drugs on this CSP . This also led to a better understanding of the chiral recognition of the CSPs regarding the studied analyte and parameters …”

HPLC‐Fluorescence Method for the Enantioselective Analysis of Propranolol in Rat Serum Using Immobilized Polysaccharide‐Based Chiral Stationary Phase

“…They help to interpret the mechanism by which the separation of enantiomers takes place and the reason for the potent biological activity of one enantiomer over the other . The analytical methods reported for chiral separation of propranolol included capillary electrophoresis methods and HPLC methods utilizing various chiral selector CSPs . However, the reported capillary electrophoresis (CE) methods were concerned with the evaluation of different chiral selectors for resolution of propranolol enantiomers using UV detection.…”

“…7,8 The analytical methods reported for chiral separation of propranolol included capillary electrophoresis methods [9][10][11] and HPLC methods utilizing various chiral selector CSPs. [12][13][14][15] However, the reported capillary electrophoresis (CE) methods were concerned with the evaluation of different chiral selectors for resolution of propranolol enantiomers using UV detection. Moreover, the chromatography methods cited for the chiral separation and determination of propranolol in biological fluids have drawbacks of low sensitivity (UV detection) and deficiency of pharmacokinetic study.…”