New approaches of LC‐MS compatible method development on α₁‐acid glycoprotein‐based stationary phase for resolution of enantiomers by HPLC

Abstract

Protein-based chiral stationary phases, in particular α(1)-acid glycoprotein, are chromatographic materials with a very broad application range. The chiral recognition ability of this selector allows the resolution of more than 90% of the molecules tested. A step-by-step description of the screening approach that we have developed is described in this article with two objectives in mind: obtaining a high success rate with a straightforward methodology that can be generally applied and allowing LC-MS compatibility. Second, the screening strategy is required to take into account the main functional nature of the racemic compound to be resolved (neutral, acidic or basic) for method optimisation step, but should be independent of other structural features, in order to allow the routine application of screening sequences and the application to the largest number of samples.

Chiral Separations: A Review of Current Topics and Trends

“…48 The analysis was found to be relatively rapid and was also employed in the measurement of the enzyme catalytic activity in the incubation of D,L-amino acids with D-amino acid oxidase and the study of the enzyme kinetics. A generalized method development screening procedure that allows LC-MS compatibility was reported by Michishita et al 49 Applications developed using protein based CSPs included enantioseparations of doxazosin on an ovomucoid column, 50 dorzolamide hydrochloride on α-1-acid glycoprotein CSP, 51 and aryloxyphenoxypropionic herbicides in soil on α-1-acid glycoprotein CSP. 52 Miscellaneous.…”

Retarded Photooxidation of Cyamemazine in Biomimetic Microenvironments

“…In the case of human AAG (HAAG) it has been concluded that PTZ derivatives bind preferentially to only one common binding site, where hydrophobic forces are mainly involved, although electrostatic interactions also participate . The affinity of PTZs for HAAG has been employed for the development of glycoprotein‐based stationary phases for the resolution of enantiomers by HPLC .…”

Chiral separation and molecular simulation study of six antihistamine agents on a coated cellulose tri‐(3,5‐dimethylphenycarbamate) column (Chiralcel OD‐RH) and its recognition mechanisms

“…HPLC‐MS/MS has become a popular analytical technique in the chiral analysis as it allows selective and sensitive measurement or identification of the compounds in synthetic sample mixtures or complex biological extracts [37–39]. The use of normal‐phase solvents, such as n ‐hexane in the mobile phase, cannot be accepted by atmospheric pressure chemical ionization and ESI interfaces connecting HPLC to MS, because the high proportion of n ‐hexane are generally incompatible with the atmospheric pressure chemical ionization or ESI source and also might raise a concern of an explosion hazard at an elevated temperature in the presence of a corona discharge or the high voltage of the electrospray needle [40,41]. Consequently, considering the MS‐compatibility and broader applicability, the reversed mode was used herein.…”