Separation of profen enantiomers by capillary electrophoresis using cyclodextrins as chiral selectors

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

“…At pH 6.0, profens, which are monoprotic weak acids (average pK a , 4.5), are fully dissociated ( 90%) and the electrophoretic mobility of each profen toward the inlet (anode) is high but its apparent mobility is toward the detector (cathode) due to the presence of higher EOF. The present MES buffer used (pH 6.0, 100 mM) at its optimum buffer capacity appeared to provide better separation of profen anions compared with the commonly used phosphate-triethanolamine buffer of pH 5.0 [10,19], which was found to yield irreproducible MTs in the enantiomeric purity determination of ketoprofen [24].…”

“…Hence, the production of active profens in enantiomerically pure forms, their optical purity control and stereoselective pharmacokinetic studies have become important tasks in the chiral drug development [4][5][6][7][8]. These tasks could be more effectively conducted in high-throughput analysis mode by simultaneous enantioseparation of multiple profens in a single run [9][10][11][12] rather than in more commonly employed individual profen analysis mode [13][14][15][16][17][18][19][20][21][22][23][24][25].…”

“…Single CD system approaches employed either uncharged CDs such as heptakis(2,3,6-tri-O-methyl)-b-CD (TMbCD) [9-11, 14, 16, 19, 21, 24], hydroxypropyl-b-CD [13,21] and cyanoethylated b-CD [18], or charged CDs such as anionic sulfated b-CD [23], cationic b-CD-heptakis(6-methoxyethylamine) [12] and permethyl-6-monoamino-6-monodexyl-b-CD (PMMAbCD) [25]. They were operated in the conventional normal polarity (NP) mode [10,14,19,24] or more preferentially in the reversed polarity (RP) mode [9, 11-13, 16, 18, 21, 23]. For the enhancement of selectivity and resolution, dual CD system approaches have been explored by combining neutral TMbCD having the highest enantioselectivity toward profens with anionic sulfobutyl-b-CD (SBbCD) or carboxymethyl-b-CD (CMbCD) [5,15,20], heptakis-6-sulfato-b-CD (HSbCD) [22,25], or cationic mono(6-amino-6-deoxy)-b-CD (bCDNH 2 ) [17].…”

“…The reversal of EMO measured in the NP mode has been carried out by reversing the enantiomer affinity pattern depending on the cavity size of CDs and on the substituents of the CD rim [30][31][32]34]. The EMOs of weakly acidic profens in a given CD system were not reversed by just selecting an appropriate combination of pH and CD concentrations [13,10]. They could be reversed by reversing the polarity of the high-voltage supply under the conditions of EOF suppression [9,13,16,18,21], EOF reversal [11], or anionic CD addition [5,8,15,20,22,23,25].…”

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.…”