[ Pharmaceutical Sciences Asia - ONLINE ]
E-ISSN 2586-8470
[ Journal Abbreviation: Pharm.Sci.Asia ]
Mahidol University Journal of Pharmaceutical Sciences
  FORMER NAME   "Mahidol University Journal of Pharmaceutical Sciences" Published Since 1974


DOI: https://doi.org/10.29090/psa.2018.02.066Pharm Sci Asia 2018; 45(2), 66-76

Development of a UPLC method with Chiral Derivatization for the Determination of Atenolol and Metoprolol Enantiomers in Tablet Preparations

N.V.T. Nguyen, D.K.T. Pham, K.N.H. Nguyen, T.T.T. Nguyen, T.L.T. Pham, T. K. Nguyen, K.H. Kim

1 Can Tho University of Medicine and Pharmacy, Vietnam
2 College of Pharmacy, Kangwon National University, Chunchon, Korea

Atenolol and metoprolol are used in the treatment of angina pectoris, certain arrhythmias, systemic hypertension, and several other cardiovascular disorders. Both compounds are produced commercially in the racemic and enantiomer, even though the S-form is responsible for the desired biological effect. The aim of this study was to development a simple, rapid chiral derivatization method for the determination of atenolol and metoprolol enantiomers in tablet preparations using chiral derivatization agent (2,3,4,6-tetraO-acetyl-?-D-glucopyranosyl isothiocyanate (GITC). The optimization of the derivatization procedure (concentration of GITC, reaction temperature and time) and UPLC conditions (pH and ionic strength of mobile phase) were investigated. With 20 times molar excess of GITC, chiral derivatization reaction was completed within 15 min at room temperature. Diastereomeric derivatives of atenolol and metoprolol were well resolved on UPLC BEH C18 column (2.1 x 100 mm, 1.7 ?m) with acetonitrile - ammonium acetate buffer as mobile phase and monitored at UV 225 nm. Separation was completed in less than 10 min. The LOD and LOQ of atenolol-GITC were 0.18 ?m/ml and 0.35 ?m/ml, respectively. The LOD and LOQ of metoprolol-GITC were 0.06 ?m/ml and 0.2 ?m/ml, respectively. The recovery of two compounds was 98-102%. The results of the studies showed that the proposed RP -UPLC method is simple, rapid, precise and accurate, which can be applied for the routine assessment of atenolol, metoprolol and their enantiomers impurity in pharmaceutical dosage forms.


Chiral derivatization reaction, metoprolol, atenolol, enantiomer, GITC

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