Fast chiral separation of drugs using columns packed with sub‐2 μm particles and ultra‐high pressure

Abstract

The use of columns packed with sub-2 lm particles in liquid chromatography with very high pressure conditions (known as UHPLC) was investigated for the fast enantioseparation of drugs. Two different procedures were evaluated and compared using amphetamine derivatives and b-blockers as model compounds. In one case, cyclodextrins (CD) were directly added to the mobile phase and chiral separations were carried out in less than 5 min. However, this strategy suffered from several drawbacks linked to column lifetime and low chromatographic efficiencies. In the other case, the analysis of enantiomers was carried out after a derivatization procedure using two different reagents, 2,3,4-tri-O-acetyl-a-D-arabinopyranosyl isothiocyanate (AITC) and N-a-(2,4-dinitro-5-fluorophenyl)-L-alaninamide (Marfey's reagent). Separation of several amphetamine derivatives contained within the same sample was achieved in 2-5 min with high efficiency and selectivity. The proposed approach was also successfully applied to the enantiomeric purity determination of (1)

Determination of methamphetamine enantiomer composition in human hair by non-chiral liquid chromatography–tandem mass spectrometry method

“…The Marfey's derivitization and the LC-MS/MS parameters were similar to previously published methods [25][26][27]. In the extracts containing the cocktail of potentially interfering substances (including amphetamine, Fig.…”

“…It reacts quickly and efficiently with primary amines generating fairly stable derivatives [24]. Marfey's reagent has also been used for successful determination of enantiomeric composition of amphetamine-like compounds in biological samples [25], including urine [26], plasma, and oral fluid [27]. These applications have proven that Marfey's reagent derivatization eliminates the requirement of chiral chromatographic separation and/or specialized detection method.…”

A high throughput approach to purifying chiral molecules using 3μm analytical chiral stationary phases via supercritical fluid chromatography

“…With SFCs low backpressure due to the low viscosity of carbon dioxide, it is a perfect fit for using small particles to increase resolution and speed. While there have been reports about using small particles for chiral analysis using normal phase approaches [17,18], we have not seen these small particles used in SFC chiral separations.…”

Sub-1-micron mesoporous silica particles functionalized with cyclodextrin derivative for rapid enantioseparations on ultra-high pressure liquid chromatography

“…In the aspect of chiral separation, there are no commercial sub-2 m chiral columns, and reports on sub-2 m particles columns are uncommon. Some works reported chiral separations using commercial sub-2 m achiral columns by adding chiral additives [22,23]. Cancelliere et al [24] erably shorter analysis time and lower solvent consumption but similar resolutions when reduced particle size and shorter columns were used.…”