Analytical and semipreparative resolution of ranolazine enantiomers by liquid chromatography using polysaccharide chiral stationary phases.
Novel HPLC methods were developed for the analytical and semipreparative resolution of new antianginal drug ranolazine enantiomers. Good baseline enantioseparation was achieved using cellulose tris (3,5-dimethylphenylcarbamate) (CDMPC) chiral stationary phases (CSPs) under both normal-phase and polar organic modes. The validation of the analytical methods including linearity, LODs, recovery, and precision, and the semipreparative resolution of ranolazine racemate were carried out using methanol as mobile phase without any basic and acidic additives under polar organic mode, using CDMPC CSPs. At analytical scale, the elution times of both enantiomers were less than 7.5 min at 20 degrees C and 1.0 mL/min, with the separation factor (a) 1.88 and the resolution factor (R(s)) 2.95. At semipreparative scale, about 14.3 mg/h enantiomers could be isolated and elution times of both enantiomers were less than 13 min at 2.0 mL/min. To increase the throughput, the technique of overlapping injections was used. The first eluted enantiomer was isolated with a purity of 99.6% enantiomer excess (e.e.) and > 99.0% yield. The second enantiomer was isolated with a purity of 98.8% e.e. and > 99.0% yield. In addition, optical rotation and circular dichroism spectroscopy of both ranolazine enantiomers isolated were also investigated.
Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, PR China.
Xingping
X
Luo
Zongde
Z
Zhai
Xiaomei
X
Wu
Yanping
Y
Shi
Liren
L
Chen
Yongmin
Y
Li
D000083:Acetanilides; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry / Q000302:isolation & purification*; D011134:Polysaccharides / Q000737:chemistry*; D000069458:Ranolazine; D015203:Reproducibility of Results; D013237:Stereoisomerism
D000083:Acetanilides; D010879:Piperazines; D011134:Polysaccharides; D000069458:Ranolazine