Enantiomeric separation of drugs and related compounds based on their interaction with α1-acid glycoprotein

Chiral stationary phases in HPLC for the stereoselective determination of methadone

“…37 The protein has a net negative charge at pH between 4 and 7, so most basic drugs with pK a values above 7 are strongly retained. 38 Moreover, several studies have reported that basic drugs are bound stereoselectively to ␣ 1 -acid glycoprotein in plasma. 37 AGP is a very stable protein and is now used as a chiral selector bonded to a chromatographic support.…”

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

“…The effect of increasing temperature on enantioseparation from ambient to ∼80°C produces enhanced efficiency with a decrease in retention. 38,47,48 Evaluation of AGP column performance at lower temperatures has not been reported. Reviews of chiral HPLC using AGP as a chiral selector have been presented.…”

“…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.…”

“…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.…”

New data on the sorption properties of ?1-acid glycoprotein chiral stationary phase

“…4 Because of its broad applicability and the use of buffered aqueous mobile phases being compatible with biological fluids, the CHIRAL-AGP column has become popular for the direct separation of the different types of enantiomers (e.g., acidic, neutral, and basic drugs). [5][6][7] Owing to the highly complex structure of the protein, the character of the chiral binding processes is only incompletely known and the choice of conditions for stereoselective separation is more or less empirical. 8,9 The organic modifiers have primarily been introduced to decrease the retention times of the highly retained analytes, but in many cases they influence the chiral selectivity as well.…”