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 AJAC  Vol.3 No.7 , July 2012
Development and Validation of Chiral HPLC Method for Identification and Quantification of (R)-Enantiomer in Ezetimibe
Abstract: A normal phase enantioselective high performance liquid chromatographic method was developed for enantiomeric resolution of Ezetimibe it reduces the overall delivery of cholesterol to the liver. The enantiomers of Ezetimibe were resolved on a Chiral Pak AS-H (250 × 4.6 mm, 5 μm) column using a mobile phase system containing n-Hexane, etha-nol, 2-Propanol and Trifloroacetic acid (84:12:4:0.1 v/v). The resolution between enantiomers was found to be more than 2.0. The limit of detection and limit of quantification of (R)-enantiomer were found to be 0.2 μg/mL and 0.5 μg/mL, respectively, for 10 μL injection volume. The sample solution and mobile phase were found to be stable for at least 48 h. The final optimized method was successfully applied to separate (R)-enantiomer from Ezetimibe and was proven to be reproducible and accurate for the quantitative determination of (R)-enantiomer in bulk drugs.
Cite this paper: K. Chimalakonda, V. Gudala, M. Gutta, S. Polisetty and S. Koduri, "Development and Validation of Chiral HPLC Method for Identification and Quantification of (R)-Enantiomer in Ezetimibe," American Journal of Analytical Chemistry, Vol. 3 No. 7, 2012, pp. 478-483. doi: 10.4236/ajac.2012.37063.
References

[1]   H. Caner, E. Groner, L. Levy and I. Agranat, “Trends in the Development of Chiral Drugs,” Drug Discovery Today, Vol. 9, No. 3, 2004, pp. 105-110. doi:10.1016/S1359-6446(03)02904-0

[2]   J. Caldwell, “Importance of Stereospecific Bionalytical Monitoring in Drug Development,” Journal of Chromatography A, Vol. 719, No. 1, 1996, pp. 3-13. doi:10.1016/0021-9673(95)00465-3

[3]   N. M. Maier, P. Franco and W. Lindner, “Separation of Enantiomers: Needs Challenges, Perspectives,” Journal of Chromatography A, Vol. 906, No. 1-2, 2001, pp. 3-33. doi:10.1016/S0021-9673(00)00532-X

[4]   T. E. Beesley and R. P. W. Scott, “Chiral Chromatography,” John Wiley & Sons, Ltd., Chichester, 1998, pp. 23- 26.

[5]   X. X. Xu, R. Fu, S. W. Chen, et al., “Ezetimibe Analogs with a Reorganized Azetidinone Ring: Design, Synthesis, and Evaluation of Cholesterol Absorption Inhibitions,” Bioorganic & Medicinal Chemistry Letter, Vol. 17, No. 1, 2007, pp. 101-104. doi:10.1016/j.bmcl.2006.09.078

[6]   E. Leitersdorf, “Selective Cholesterol Absorption Inhibition: A Novel Strategy in Lipid-Lowering Management,” International Journal of Clinical Practice, Vol. 56, No. 2, 2002, pp. 116-119.

[7]   M. Van Heek, C. Farley and D. S. Compton, “Ezetimibe Selectively Inhibits Intestinal Cholesterol Absorption in Rodents in Presence and Absence of Exocrine Pancreatic Function,” British Journal of Pharmacology, Vol. 134, No. 2, 2001, pp. 409-417. doi:10.1038/sj.bjp.0704260

[8]   S. Singh, B. Singh, R. Bahuguna, L. Wadhwa and R. Saxena, “Stress Degradation Studies on Ezetimibe and Development of a Validated Stability-Indicating HPLC Assay,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 41, No. 3, 2006, pp. 1037-1040. doi:10.1016/j.jpba.2006.01.030

[9]   R. Sistla, V. S. Tata, Y. V. Kashyap, D. Chandrasekar and P. V. Diwan, “Development and Validation of a Reversed-Phase HPLC Method for the Determination of Ezetimibe in Pharmaceutical Dosage Forms. Journal of Pharmaceutical and Biomedical Analysis, Vol. 39, No. 3-4, 2005, pp. 517-522. doi:10.1016/j.jpba.2005.04.026

[10]   B. G. Chaudhari, N. M. Patel and P. B. Shah, “Stability-Indicating Reversed-Phase Liquid Chromatographic Method for Simultaneous Determination of Simvastatin and Ezetimibe from Their Combination Drug Products,” Journal of AOAC International, Vol. 90, No. 5, 2007, pp. 1242-1249.

 
 
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