Enantioseparation of Palonosetron Hydrochloride and Its Related Enantiomeric Impurities by Computer Simulation and Validation


A rapid, simple and single stereo selective high-performance liquid chromatographic (HPLC) method was developed and validated for enantiomers of palonosetron hydrochloride (PALO) and its process related chiral impurities. A computer simulating software was used for the development of chiral method. The developed method was able to separate not only the enantiomers of palonosetron hydrochloride but also its process related chiral impurities within 12 min. The chromatographic separation was carried out by normal phase chromatography using a 3 µm column of cellulose based chiral stationary phase (Chiralcel-OD 250mm × 4.6mm) with a mobile phase comprised of n-hexane: ethanol: methanol: heptafluoro butyric acid: diethyl amine (70:15:15:0.05:0.1, v/v) at a flow rate of 1.0 mL/min. The effects of additive concentration as well as nature of polar organic modifier, flow rate, and temperature on enantioselectivity were investigated. The limit of detection (LOD) and limit of quantification (LOQ) of the palonosetron isomers and its related chiral impurities were found to be in the range 0.06-0.10 µg/mL and 0.14 - 0.24 µg/mL respectively. The method showed excellent linearity (R2 > 0.998) over a range of 0.14 to 1.125 µg/mL. The percentage recovery of the isomers in bulk drug samples ranged from 87.0 to 116.0.

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M. Murthy, C. Krishnaiah, K. Jyothirmayi, K. Srinivas, K. Mukkanti, R. Kumar and G. samanta, "Enantioseparation of Palonosetron Hydrochloride and Its Related Enantiomeric Impurities by Computer Simulation and Validation," American Journal of Analytical Chemistry, Vol. 2 No. 4, 2011, pp. 437-446. doi: 10.4236/ajac.2011.24053.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. D. Wit, M. Aapro and P.R. Blower, “Is There a Phar-macological Basis for Differences in 5-HT3-Receptor Antagonist Efficacy in Refractory Patients?” Cancer Chemotherapy and Pharmacology, Vol. 56, No. 3, 2005, pp. 231-238. doi:10.1007/s00280-005-1033-0
[2] M. Aapro and P. Blower, “5-Hydroxytryptamine Type-3 Receptor Antagonists for Chemotherapy-Induced and Radiotherapy-Induced Nausea and Emesis: Can We Safely Reduce the Dose of Administered Agents?” Cancer, Vol. 104, No. 1, 2005, pp. 1-13. doi:10.1002/cncr.21141
[3] J. T. Hickok, J. A. Roscoe, G. R. Morrow, C. W. Bole, H. W. Zhao, K. L. Hoelzer, S. R. Dakhil, T. Moore and T. R. Fitch, “5-Hydroxytryptamine-Receptor Antagonists versus Prochlorperazine for Control of Delayed Nausea Caused by Doxorubicin: A URCC CCOP Randomised Controlled Trial,” The Lancet Oncology, Vol. 6, No. 10, 2005, pp. 765-772. doi:10.1016/S1470-2045(05)70325-9
[4] P. Eisenberg, J. F.Vadillo, R. Zamora, V. Charu, J. Haj-denberg, A. Cartmell, A. Macciocchi and S. Grunberg, “Improved Prevention of Moderately Emetogenic Che-motherapy-Induced Nausea and Vomiting with Palonose-tron, a Pharmacologically Novel 5-HT3 Receptor Anta-gonist. Results of a Phase III, Single-Dose Trial versus Dolasetron,” Cancer, Vol. 98, No. 11, 2003, pp. 2473- 2482. doi:10.1002/cncr.11817
[5] http://www.rxlist.com/aloxi-drug.htm accessed January 2009.
[6] M. Wang, X. Ding, H. Chen and X. Chen, “Enantiosepa-ration of Palonosetron Hydrochloride by Capillary Zone Electrophoresis with High-Concentration β-CD as Chiral Selector,” Analytical Sciences, Vol. 25, No. 10, 2009, pp. 1217-1220. doi:10.2116/analsci.25.1217
[7] K. Tian, H. Chen, J. Tang, X. Chen and Z. Hu, “Enanti-oseparation of Palonosetron Hydrochloride by Micellar Electrokinetic Chromatography with Sodium Cholate as Chiral Selector,” Journal of Chromatography A, Vol. 1132, No. 325, 2006, pp. 333-336. doi:10.1016/j.chroma.2006.08.090
[8] P. Radhakrishnanand, D. V. Subba Rao and V. Himabin-du, “Validated Chiral LC Method for the Enantiomeric Separation of Palonosetron Hydrochloride,” Chromato-graphia, Vol. 69, No. 3-4, 2009, pp. 369-373. doi:10.1365/s10337-008-0887-9
[9] X.-R. Yu, M. Song and T.-J. Hang, “Direct Enantiomeric Separation of Palonosetron Hydrochloride by Chiral HPLC,” Chinese Journal of New Drugs, Vol. 10, 2008, p. 16.
[10] J. W. Dolan, L. R. Snyder, N. M. Djordjevic, D. W. Hill and T. J. Waeghe, “Reversed-Phase Liquid Chromato-graphic Separation of Complex Samples by Optimizing Temperature and Gradient Time: I. Peak Capacity Limi-tations,” Journal of Chromatography A, Vol. 857, 1999, pp. 1-20. doi:10.1016/S0021-9673(99)00765-7
[11] J. W. Dolan, L. R. Snyder, N. M. Djordjevic, D. W. Hill, D. L. Saunders, L. Van Heuhelem and T. J. Waeghe, “Simultaneous Variation of Temperature and Gradient Steepness for Reversed-Phase High-Performance Liquid Chromatography Method Development: I. Application to 14 Different Samples Using Computer Simulation,” Journal of Chromatography A, Vol. 803, 1998, pp. 1-31.
[12] R. G. Wolcott, J. W. Dolan and L. R. Snyder, “Computer Simulation for the Convenient Optimization of Isocratic Reversed-Phase Liquid Chromatographic Separations by Varying Temperature and Mobile Phase Strength,” Jour-nal of Chromatography A, Vol. 869, No. 1-2, 2000, pp. 3-25. doi:10.1016/S0021-9673(99)00876-6
[13] ICH, “Stability Testing of New Drug Substances and Products (Q1AR2),” ICH Harmonized Tripartite Guideline.

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