Separation of the enantiomers of β-receptor blocking agents and other cationic drugs using a CHIRAL-AGP® column

Cromatografia líquida com fase quiral aplicada na separação enantiomérica de fármacos cardiovasculares

“…Para tanto, foram utilizadas duas fases estacionárias quirais uma derivada de celulose (Chiralcel OD ® ) (Figura 2) e a outra derivada de dinitrobenzoila (α-Burke 2 ® ) (Figura 3). Recentemente, alguns pesquisadores empregaram cromatografia líquida de alta eficiência com colunas dos tipos Chiralcel OD ® (Balmer et al, 1991;Ching et al, 1989;Ekelund et al, 1995;Herring, Bastian, Lalonde, 1991;Krstulovic, 1988;Rutledge, Garrick, 1989;Straka et al, 1990;Zhang, Stewart, Ujhelyi, 1995), β-ciclodextrina (Ekelund et al, 1995;He et al, 1993;Ward, Armstrong, 1988) e α-1-ácido glicoproteína (AGP) (Berthault, Kintz, Mangin, 1997;Ceccato, Hubert, Crommen, 1997;Enquist, Hermansson, 1990;Hermansson, Von Bahr, 1982;Svensson, Vessman, Karlsson, 1999) e antibiótico macrocíclico (teicoplanina -Chirobiotic T ® ) (Lamprecht et al, 2000;Mistry, Leslie, Eddington, 2001) para a determinação enantiomérica dos FIGURA 1 -Estrutura química dos β-bloqueadores. β-bloqueadores.…”

Mechanistic aspects of chiral discrimination by surface-immobilized ?1-acid glycoprotein

“…The lack of information concerning the tertiary structure of AGP and the groups involved in solute binding suggests that no general rules can yet be given regarding the required solute structural features for HPLC enantioselective separation. 46 However, some structural and steric correlations with separation have been proposed 37,42,45,47 which may predict a successful enantioseparation. The effect of increasing temperature on enantioseparation from ambient to ∼80°C produces enhanced efficiency with a decrease in retention.…”

“…Varying mobile phase compositions, pH, modifiers, and buffers have provided separations reportedly influenced by apolar interactions, 31,37,42,43 hydrogen bonding, 44 ionic bonding, and ionpairing. 32,37,43 It has been suggested that enantioselectivity is the result of solute interaction with a hydrophobic core 1,38,45 of the immobilized AGP by analogy to the interaction of drug binding to native AGP. The lack of information concerning the tertiary structure of AGP and the groups involved in solute binding suggests that no general rules can yet be given regarding the required solute structural features for HPLC enantioselective separation.…”

“…36 Although it is possible that the conformation of AGP is altered upon immobilization on a chromatographic support, there is evidence that AGP maintains many of its native properties. 37 The utility of AGP columns in providing chiral separations for a number of basic, neutral and acidic compounds suggests that multiple binding mechanisms may exist. 31,32,37 Reversible conformational changes influenced by mobile phase pH and modifiers [38][39][40][41] have been proposed to be involved in the enantioselectivity of these protein based columns.…”

“…37 The utility of AGP columns in providing chiral separations for a number of basic, neutral and acidic compounds suggests that multiple binding mechanisms may exist. 31,32,37 Reversible conformational changes influenced by mobile phase pH and modifiers [38][39][40][41] have been proposed to be involved in the enantioselectivity of these protein based columns. Varying mobile phase compositions, pH, modifiers, and buffers have provided separations reportedly influenced by apolar interactions, 31,37,42,43 hydrogen bonding, 44 ionic bonding, and ionpairing.…”