Indirect reversed-phase high-performance liquid chromatographic and direct thin-layer chromatographic enantioresolution of (R,S)-Cinacalcet.
Enantioresolution of the calcimimetic drug (R,S)-Cinacalcet was achieved using both indirect and direct approaches. Six chiral variants of Marfey's reagent having L-Ala-NH(2), L-Phe-NH(2), L-Val-NH(2), L-Leu-NH(2), L-Met-NH(2) and D-Phg-NH(2) as chiral auxiliaries were used as derivatizing reagents under microwave irradiation. Derivatization conditions were optimized. Reversed-phase high-performance liquid chromatography was successful using binary mixtures of aqueous trifluoroacetic acid and acetonitrile for separation of diastereomeric pairs with detection at 340 nm. Thin silica gel layers impregnated with optically pure L-histidine and L-arginine were used for direct resolution of enantiomers. The limit of detection was found to be 60 pmol in HPLC while in TLC it was found to be in the range of 0.26-0.28 µg for each enantiomers.
Bhushan
Ravi
R
Department of Chemistry, Indian Institute of Technology Roorkee, India. rbushfcy@iitr.ernet.in
Dubey
Rituraj
R
D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D001120:Arginine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D002855:Chromatography, Thin Layer / Q000379:methods*; D000069449:Cinacalcet; D004136:Dinitrobenzenes / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D009281:Naphthalenes / Q000737:chemistry* / Q000302:isolation & purification; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013696:Temperature
D004136:Dinitrobenzenes; D009281:Naphthalenes; D006639:Histidine; D001120:Arginine; C047134:Marfey's reagent; D000409:Alanine; D000069449:Cinacalcet