Sub- and Supercritical Fluid Chromatography on Packed Columns: A Versatile Tool for the Enantioselective Separation of Basic and Acidic Drugs

Abstract

Various chiral stationary phases were investigated in sub- and supercritical fluid chromatography for the separation, without derivatization, of basic (beta-blockers, benzodiazepines) and acidic (nonsteroidal anti-inflammatory drugs, beta-agonists) pharmaca. For all racemates, baseline separation was achieved within short analysis times. For several solutes, the high resolution obtained allowed injection of milligram amounts and semipreparative collection of the enantiomers. The parameters affecting enantioselectivity (column efficiency, influence of modifiers and basic or acidic additives, and temperature) have been studied. Enantiomerization of 3-OH-benzodiazepines could be suppressed by working at low temperatures or by using acetonitrile as a comodifier. Serial coupling of different chiral stationary phase columns resulted in a column triplet (Chiralpak AD, an amylose derivative; Chiralcel OD, a cellulose derivative; and Chirex 3022, a Brush-type with pi-donor characteristics) on which all solutes investigated could be baseline separated.

Sub- and Supercritical Chiral Separation of Racemic Compounds on Columns with Stationary Phases Having Different Functional Groups

“…Amino groups in basic compounds are prevented from interacting with the CSP by the formation of carbonate. Moreover, since alcohol modifiers are often not sufficiently strong to deactivate the surface properly, 25) basic or acidic additives are added to the mobile phase to improve the peak shape by masking the active sites of the support material. Diethylamine (DEA) was selected as an additive in this study to maintain the free amino function of the test compounds and mask the surface of the silica-gel support.…”

Peer Reviewed: SFC of Drug Enantiomers.

“…Column coupling. A single CSP may not always provide the necessary separation, but the reduced pressure drop in SFC makes it easy to couple similar or dissimilar stationary phases (34,35 ). Combining CSPs of the same type can increase marginal enantioresolution to an acceptable level.…”

Correlation Equation for Retention Factor and Resolution of Ibuprofen in SFC

“…9 And several supercritical fluid chromatographic methods involving a various chiral stationary phase has been reviewed. [10][11][12][13][14][15][16][17] The purpose of this study is to develop an optimum SFC separation method for the chiral separation of ibuprofen by investigating the different factors, such as pressure, temperature and the content of IPA in the supercritical fluid mobile phase. And several potential empirical equation of retention factor and resolution will be suggested for the prediction of the parameters.…”