Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Back
Research Article

A New Stability-indicating Chiral RP-HPLC Method for the Determination of Degradation Products in Meclizine Hydrochloride

Author(s): Bryan Gowramma*, Ramachandran Senthil Kumar, Kaviarasan Lakshmanan, Rajagopal Kalirajan and Subramania Nainar Meyyanathan

Volume 17, Issue 8, 2021

Published on: 30 June, 2020

Page: [1075 - 1087] Pages: 13

DOI: 10.2174/1573412916999200630123802

Price: $65

Abstract

Background: An enantiomeric separation of the stability-indicating high-performance liquid chromatographic method was developed and validated for the analysis of Meclizine enantiomers. The degradation behavior of Meclizine Hydrochloride was investigated under different stress conditions recommended by the International Conference on Harmonization (ICH).

Methods: Enantiomeric resolution of the drug and complete separation from its degradation products were successfully achieved on a Phenomenex® lux cellulose 1 C18 (250 mm × 4.6 mm i.d, 5 μm particle size) column, using UV detector at a wavelength of 230 nm, with a mobile phase consisting of acetonitrile, 20mM ammonium bicarbonate at the ratio of 75:25 (v/v), and a flow rate of 1 mL/min. The drug was subjected to alkaline, acidic, neutral, oxidative and photolytic conditions in order to mimic stress conditions.

Results: The degradation products were well resolved from the main peak, proving the stabilityindicating power of the method. The developed method provided linear responses within the concentration range of 1-5 μg/mL, and regression analysis showed a correlation coefficient value (r2) of 0.999. The HPLC method was validated as per ICH guidelines with respect to specificity, precision, linearity and robustness. Limit of Detection (LOD) and Limit of Quantification (LOQ) were found to be 0.25 μg/mL and 1.00 μg/mL, respectively.

Conclusion: The method provides good sensitivity and excellent precision and reproducibility. The method was highly selective, in which degradation products and co-formulated compounds did not interfere. The proposed method was successfully applied in pharmaceutical preparations.

Keywords: Meclizine hydrochloride, enantiomers, chirality, RP-HPLC, ICH, validation, chiral, RP-HPLC, stability-indicating method.

« Previous Next »
Graphical Abstract

[1]
Ho, Y.; Wu, H.; Wu, S.; Chen, S.; Kou, H. Quantitative enantiomeric analysis of chlorcyclizine, hydroxyzine, and meclizine by capillary electrophoresis. Anal. Bioanal. Chem., 2003, 376(6), 859-863.
[http://dx.doi.org/10.1007/s00216-003-2015-x] [PMID: 12830360]
[2]
Eto, S.; Noda, H.; Noda, A. High-performance liquid chromatographic method for direct separation of 5-(p-hydroxyphenyl)-5-phenylhydantoin enantiomers using a chiral tris(4-methylbenzoate) column. J. Chromatogr. A, 1991, 568(1), 157-163.
[http://dx.doi.org/10.1016/0378-4347(91)80349-H] [PMID: 1770093]
[3]
Hassan, Y.; Aboul, E.; Rafiqul, I.M. Enantiomeric separation of ketamine hydrochloride in pharmaceutical formulation and human serum by chiral liquid chromatography. J. Liq. Chromatogr., 1992, 15(18), 3285-3293.
[http://dx.doi.org/10.1080/10826079208020884]
[4]
Hardmann, J.G.; Limbird, L.E.; Molinoff, P.B.; Ruddon, R.W.; Gilmann, A.G., Eds.; Goodman & Gilman’s the pharmacological basis of therapeutics; New York: McGraw-Hill, 1996.
[5]
Witte, D.T. High performance liquid chromatography for direct and indirect method for enantiomeric separation of chiral drugs. Pharm. World Sci., 1993, 15(6), 283-284.
[http://dx.doi.org/10.1007/BF01871133]
[6]
Kelly, J.W.; He, L.; Stewart, J.T. Liquid chromatographic separation of praziquantel enantiomers in serum using a cellulose-based chiral stationary phase. J. Pharm. Biomed. Anal., 1993, 11(11-12), 1141-1144.
[http://dx.doi.org/10.1016/0731-7085(93)80095-I] [PMID: 8123726]
[7]
Makoto, T.; Hideki, Y.; Hideo, H. Direct HPLC separation of enantiomers of pantoprazole and other benzimidazole sulfoxides using cellulose-based chiral stationary phases in reversed-phase mode. Chirality, 1995, 7(8), 612-615.
[http://dx.doi.org/10.1002/chir.530070810]
[8]
Jacek, B.; Hassan, Y.; Aboul, E.; Ashraf, G. What’s new in chromatographic enantio separations. Curr. Anal. Chem., 2005, 1, 59-77.
[http://dx.doi.org/10.2174/1573411052948433]
[9]
Madhusudhan, S.; James, T.S. Enantiomeric HPLC separations of chiral local anesthetics using cellulose based chiral stationary phases. Anal. Lett., 1997, 30(6), 1167-1178.
[http://dx.doi.org/10.1080/00032719708004046]
[10]
Selditz, U.; Liao, Y.; Franke, J.P.; de Zeeuw, R.A.; Wikström, H. Direct enantiomeric separation of mianserin and 6-azamianserin derivatives using chiral stationary phases. J. Chromatogr. A, 1998, 803(1-2), 169-177.
[http://dx.doi.org/10.1016/S0021-9673(97)01288-0] [PMID: 9634278]
[11]
Kumar, V.P.; Christopher, D.R.; Saul, W.F. Development of reversed-phase chiral HPLC methods using mass spectrometry compatible mobile phases. J. Liq. Chromatogr. Relat. Technol., 2000, 23(6), 831-839.
[http://dx.doi.org/10.1081/JLC-100101492]
[12]
Reynolds, D.W.; Facchine, K.L.; Mullaney, J.F.; Alsante, K.M.; Hatajik, T.D.; Motto, M.G. Available guidance and best practices for conducting forced degradation studies. Pharm. Technol., 2002, 26(2), 48-56.
[13]
Reynolds, D.W. Forced degradation of pharmaceuticals. Am. Pharmaceut. Rev., 2004, 7(3), 56-61.
[14]
Thatcher, S.R.; Mansfield, R.K.; Miller, R.B.; Davis, C.W.; Baertschi, S.W. Pharmaceutical photostability. Pharm. Technol., 2001, 25(3), 98-110.
[15]
Kats, M. Forced degradation studies: regulatory considerations and implementation. Biopharm Int., 2005, 18, 7.
[16]
Alsante, KM; Ando, A; Brown, R The role of degradant profiling in active pharmaceutical ingredients and drug products. Adv. Drug Deliv. Rev., 2007, 59(1), 29-37.
[http://dx.doi.org/10.1016/j.addr.2006.10.006] [PMID: 17187892]
[17]
Sethi, P.D. High performance liquid chromatography. 1st ed. New Delhi 2001. pp. 5-59, 117-151.
[18]
Jinno, K. Chromatographic separations based on molecular recognition; New York, 1997, pp. 1-66.
[19]
Marvin, C. McMaster LC/MS A practical User’s Guide; New Jersey: John Wiley & Sons, 2005, pp. 1-58.
[20]
ICH. Q2A. Text on validation of analytical procedures International Conference on Harmonization.
[21]
ICH. Q3B validation of analytical procedures: methodology International Conference on Harmonization.

Rights & Permissions Print Cite
Article Metrics
23
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy