Enantiomeric separations of amino alcohols by packed-column SFC on Hypercarb with L-(+)-tartaric acid as chiral selector.
The use of L-(+)-tartaric acid as a chiral mobile phase additive (CMPA) has been investigated in a packed-column SFC system. The CMPA, carbon dioxide, and methanol, containing a high concentration of aliphatic amine additive, were used as the mobile phase and Hypercarb as support [Gyllenhaal O., Karlsson A., SFC of metoprolol and other amino alcohols on Hypercarb (in preparation)]. Good enantioselectivities were obtained for tertiary amine homologues of 2-amino alcohols, used as beta-adrenoreceptor-blocking drugs. Moderate selectivities were observed for aromatic compounds having a second substituent in the ortho-position. The overall retention was influenced by the aromaticity of the analytes as well as the presence of free electron pairs in the molecule. Increased concentrations of CMPA gave higher retention and also increased the enantioselectivity. The practical utility of this present enantioselective system was demonstrated on one batch of (S)-metoprolol that was N-methylated with methyl iodide. The enantiomeric separation was accomplished within 10 min.
Gyllenhaal
Olle
O
Analytical Chemistry, Pharmaceutical R&D, AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden. olle.gyllenhaal@astrazeneca.com
Karlsson
Anders
A
D000605:Amino Alcohols / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification*; D025924:Chromatography, Supercritical Fluid / Q000295:instrumentation / Q000379:methods*; D006108:Graphite; D008790:Metoprolol / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D008956:Models, Chemical; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013644:Tartrates; D013696:Temperature
D000605:Amino Alcohols; D013644:Tartrates; D006108:Graphite; D008790:Metoprolol; C029768:tartaric acid