Archives of Pharmacal Research
- Volume 22 Issue 6
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- Pages.614-618
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- 1999
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- 0253-6269(pISSN)
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- 1976-3786(eISSN)
Chiral Purity Test of Metoprolol Enantiomer After Derivatization with (-)-Menthyl Chloroformate by Reversed-Phase High Performance Liquid Chromatography
- Kim, Kyeong-Ho (College of Pharmacy, Kangwon National University) ;
- Choi, Pok-Wha (College of Pharmacy, Kangwon National University) ;
- Hong, Seon-Pyo (College of Pharmacy, Kyung Hee University) ;
- Kim, Hyun-Ju (College of Pharmacy, Kangwon National University)
- Published : 1999.12.01
Abstract
A reversed-phase high-performace 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 form the these two independent separation systems were compared with trace racemization and were in very good agreement. No racemization was found during the experiment.