Chiral purity test of metoprolol enantiomer after derivatization with (-)-menthyl chloroformate by reversed-phase high performance liquid chromatography.
A reversed-phase high-performance liquid chromatographic method was developed to determine the optical purity of metoprolol enantiomers. The enantiomers were converted to diastereomeric derivatives using (-)-menthyl chloroformate reagent. Separation of the enantiomers as diastereomers was achieved by reversed-phase HPLC within 30 min using Inertsil C8 column. This method allowed determination of 0.05% of either enantiomer in the presence of its stereoisomer and method validation showed adequate linearity over the required range. Owing to the reaction condition during the derivatization with (-)-menthyl chloroformate, the possibility of racemization had to be established. Different ratios of (S)-(-)-metoprolol and (R)-(+)-metoprolol were prepared. Enantiomeric separation of these mixtures took place on a chiralcel OD column or, after derivatization with (-)-menthyl chloroformate, on a C8 column. The results from the these two independent separation systems were compared with trace racemization and were in very good agreement. No racemization was found during the experiment.
Kim
K H
KH
College of Pharmacy, Kangwon National University, Chunchon, Korea. Kyeong@cc.kangwon.ac.kr
Choi
P W
PW
Hong
S P
SP
Kim
H J
HJ
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005561:Formates / Q000737:chemistry*; D008790:Metoprolol / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D005561:Formates; C059663:menthyl chloroformate; D008790:Metoprolol