Chiral derivatization for separation of racemic amino and thiol drugs by liquid chromatography and capillary electrophoresis

AbstractSeparation of racemic amino drugs (α‐methylbenzeneethanamine, 6‐amino‐2‐methyl‐2‐heptanol and 1‐aminoethyl‐benzenemethanol) and thiol drugs [N‐(2‐mercapto‐1‐oxopropyl) glycine, 2‐mercaptopropanoic acid, and N‐acetyl‐3‐mercaptovaline] has been evaluated after derivatization. ortho‐Phthalaldehyde (OPA) and naphthalene‐2,3‐dicarboxaldehyde (NDA) were used with either homochiral thiols (N‐acetyl‐L‐cysteine and N‐acetyl‐D‐penicillamine) or amines [(‐)‐(1R,2S)‐norephedrine, L‐phenylalanine, L‐tyrosine, and 3‐hydroxy‐L‐tyrosine] as chiral selectors according to the analyte reactive group. The resulting 36 diastereoisomeric derivatives were studied using reversed‐phase high‐performance liquid chromatography (RP‐HPLC) and capillary electrophoresis (CE). Of the CE modes, micellar electrokinetic chromatography (MEKC) using sodium dodecyl sulfate (SDS) as surfactant, β‐cyclodextrin (β‐CD)‐modified capillary zone electrophoresis (β‐CD‐CZE), and β‐CD‐MEKC were applied. Results highlight respective performance of the reagents and separative techniques. All OPA derivatives of racemic amino drugs were resolved either by MEKC or β‐CD‐MEKC. In the case of racemic thiol drugs, 10 of the 12 OPA derivatives were resolved in β‐CD‐CZE. © 1995 Wiley‐Liss, Inc.