Simultaneous chiral discrimination of multiple profens by cyclodextrin‐modified capillary electrophoresis in normal and reversed polarity modes

Abstract

Simultaneous enantioseparations of nine profens for their accurate chiral discrimination were achieved by capillary electrophoresis (CE) in the normal polarity (NP) mode with a single cyclodextrin (CD) system and in the reversed polarity (RP) mode with a dual CD system. The single CD system in the NP mode employed heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMbetaCD) added at 75 mM-100 mM 2-(N-morpholino)ethanesulfonic acid buffer (pH 6.0) as the optimum run buffer. The dual CD system operated in the RP mode used 30 mM TMbetaCD and 1.0% anionic carboxymethyl-beta-cyclodextrin dissolved in pH 3.0, 100 mM phosphoric acid-triethanolamine buffer containing 0.01% hexadimethrine bromide added to reverse the electroosmotic flow. Fairly good enantiomeric resolutions and the opposite enantiomer migration orders were achieved in the two modes. Relative migration times to internal standard under respective optimum conditions were characteristic of each enantiomer with good precision (< 2% relative standard deviation, RSD), thereby enabling to crosscheck the chemical identification of profens and also their accurate chiralities. The method linearity in the two modes was found to be adequate (r > or = 0.9991) for the chiral assay of the profens investigated. Simultaneous enantiomeric purity test of ibuprofen, ketoprofen and flurbiprofen in a mixture was feasible in a single analysis by the present method.

Enantioselective Pharmacokinetics of Ibuprofen and Involved Mechanisms

“…The electrokinetic chromatography method seemed to be acceptable at an analytical time of 10 minutes (Jabor et al, 2002). The highperformance capillary electrophoresis method has also been successfully developed for chiral determination of ketoprofen and flubiprofen (Glowka and Karazniewicz, 2004), and for simultaneous discrimination of multiple profens (La et al, 2003). Considering the same molecular structures of 2-arylpropionic acid derivatives, methods developed for one of them could be applied to others after minor modification.…”

Effect of the chiral discrimination on the vibrational properties of (R)-, (S)- and (R,S)-ibuprofen/methyl-β-cyclodextrin inclusion complexes

“…This information is the basic knowledge needed for a rational development of the appropriate method for the resolution of racemate. In particular, cyclodextrins (CDs), which are chiral macrocycles characterized by a hydrophobic inner cavity and a outer hydrophilic surface, have been used as chiral selectors for the separation of IBP enantiomers [12][13][14][15]. In this sense, a 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 shown that, in liquid phase, (S)-IBP forms more stable inclusion complexes with hydroxyprophyl-β-cyclodextrin (HP-β-CD) as compared with (R, S)-IBP [16], as well as chiral discrimination was studied in water by NMR analysis.…”

Chiral Profiling Analysis of β‐Blockers by Capillary Electrophoresis Using Dual Chiral Selectors

“…The CE system was equipped with a photodiode array detector, an automatic injector, and an uncoated fused silica capillary (Polymicro Technologies, AZ, USA; 502 mm × 50 µm I.D. ; 400 mm to detector window) installed inside a fluid‐cooled column cartridge . Samples ( ~ 3.2 nL) were introduced in pressure injection mode for 3 s at 3.4 kPa into the capillary.…”

“…Furthermore, the chiral profiling analysis of eight β‐blockers in a single run is attempted with dual chiral selectors of uncharged DM‐β‐CD and (+)‐ or (−)‐18‐C‐6‐TA in a chiral CE system of normal polarity mode, respectively. The present method is optimized for the overall procedure and validated for accurate peak identification and chiral discrimination by crosschecking for relative migration times (RMTs) and EMOs of the investigated ( S )‐ and ( R )‐β‐blockers …”