Research Article | Volume: 8, Issue: 8, August, 2018

Separation, Quantification and Control of Enatiomers of the Key Starting Material of Dextromethorphan Hydrobromide

Ajit Anerao,  Vishal Solase,  Amol More,  Nitin Pradhan   
Ajit Anerao, Vishal Solase, Amol More, Nitin Pradhan

R&D Centre (API), Wanbury Ltd., EL-16, TTC Industrial Estate, Mahape, Navi Mumbai 400710, India.

Open Access   

Published:  Aug 31, 2018

DOI: 10.7324/JAPS.2018.8805
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Abstract

Objective: Enantiomeric resolution of racemic 1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline, a key starting material in the synthesis of the antitussive agent dextromethorphan hydrobromide. Material and method: Chiral liquid chromatographic method is developed and enantiomers are resolved on a Chiralpak ID-3 column using gradient mode of elution. Mobile phase A and B containing a mixture of 0.1% diethylamine in acetonitrile and 0.1% diethylamine in methanol respectively are optimized with the timed programme. The flow rate is 1.0 mL/minute and the column temperature was maintained at 40°C. Ultraviolet detection was performed at 280 nm wavelength and the injection volume was 20 μL. Results: The resolution between the enantiomers is found to be more than 2.5. The developed method is extensively validated and proved to be robust. The limit of detection and limit of quantification of unwanted (R)-enantiomer is found to be 0.0075% and 0.025% with respect to test concentration, respectively. The percentage recovery of (R)-enantiomer is ranged from 88.6 to 106.6 in (S)-(-)-1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8- octahydroisoquinoline sample solution. Conclusion: The proposed method is found to be suitable and accurate for the quantitative determination of (R)-enantiomer in the key starting material of the dextromethorphan hydrobromide bulk drugs.


Keyword:     HPLC chiral purity dextromethorphandevelopment validation.

Citation:

Anerao A, Solase V, More A, Pradhan N. Separation, Quantification and Control of Enatiomers of the Key Starting Material of Dextromethorphan Hydrobromide. J App Pharm Sci, 2018; 8(08): 032-038.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Reference

Bortolotti F, Bertaso A, Gottardo R, Musile G, Tagliaro F. Dextromethorphan/Levomethorphan issues in a case of Opiate overdoe. Drug Test and Ana, 2013; 5:781-784. https://doi.org/10.1002/dta.1577

CAS. Chemical Abstracts Service. 2018; Available at: http:// www.chemnet.com/cas/supplier.cgi?terms=30356-07-1&l=en&exact=dict &f=plist&mark=&submit.x=0&submit.y=0 [Accessed 12 Jan 2018].

Cersósimo M, Micheli F. Antiglutamatergic drugs in the treatment of Parkinson's disease. Handbook of Clinical Neurology. 2007; 84: 127-136. https://doi.org/10.1016/S0072-9752(07)84036-X

Divi et al. Resolution of 1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8- octahydroisoquinoline. Patent No. US 8,148,257 B1. 2012.

Demian et al. Separation of Enantiomers of Octahydroisoquinoline. Patent No. US 006063925 A. 2000.

EP 9.0. Dextromethorphan hydrobromide. The European Directorate for the Quality of Medicines & HealthCare, 2017; 2233-2234.

Guangyue Li, Peiyuan Y, Peiqian C, Jie R, Lei W, Jinhui F, Peter C, Qiaqing W, Dunming Z. New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates. Sci. Rep. 2016; ID 24973.

ICH. Impurities in new drug substances. Q3A(R2). ICH harmonised tripartite guideline. 2006.

ICH. Validation of analytical procedures: Text and methodology. Q2 (R1). ICH Harmonised Tripartite Guideline. 2005.

Kikura R., Kawamura M, Miyajima A, Sunouchi M, Goda Y. Chiral analyses of dextromethorphan/levomethorphan and their metabolites in rat and human samples using LC-MS/MS. Anal. Bioanal Chem, 2011; 400:165-74. https://doi.org/10.1007/s00216-011-4707-y

Krait S, Heuermann M, Scriba G. Development of a capillary electrophoresis method for the determination of the chiral purity of dextromethorphan by a dual selector system using quality by design methodology. J Sep Sci, 2018; 41:1405-1413. https://doi.org/10.1002/jssc.201701166

Lurie I, Kimberly A. Rapid Chiral Separation of Dextro- and Levo- Methorphan using Capillary. Electrophoresis with Dynamically Coated Capillaries. Microgram J, 2005. 3:138-141; Available at: http://forendex. safs1966.org/uploads/references/MicrogramJournal/3.3-4.138.141.pdf [Accessed 05 Feb 2018].

Magellan Rx Management. Cough and Cold Therapeutic Class Review. 2016; Available at: https://hhs.texas.gov/sites/default/ files/documents/about-hhs/communications-events/meetings-events/ dur/042817-4o.pdf [Accessed 05 Feb 2018].

Nuedexta. Dextromethorphan. EMA/CHMP/80029/2013. European Medicines Agency. EMA. 2013.

PDR. Dextromethorphan hydrobromide-Drug summary. Prescribers Digital Reference. 2018; Available at: http://www.pdr.net/ drug-summary/Maximum-Strength-Mucinex-DM-dextromethorphan-hydrobromide-guaifenesin-2165 [Accessed 21 Jan 2018].

Pharmeuropa. Dextromethorphan hydrobromide Monohydrate. Reference: PA/PH/Exp. 11/T (17) 98 ANP. The European Directorate for the Quality of Medicines & HealthCare, 2017; 2233-2234; Available at: http://pharmeuropa.edqm.eu/TextsForComment [Accessed 02 Jan 2018].

Rxlist. 2017. Available at: https://www.rxlist.com/nuedexta-drug.htm [Accessed 05 Jan 2018].

Sigma-Aldrich. 2018; Available at: https://www.sigmaaldrich. com/catalog/product/aldrich/539007?lang=en®ion=IN [Accessed 21 Jan 2018].

USP 40. Dextromethorphan hydrobromide. The United States Pharmacopeial Convention, 2017; 3705-3707.

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