ICH guidance in practice: Degradation behaviour of oseltamivir phosphate under stress conditions

Journal of Pharmaceutical and Biomedical Analysis

Volumn 62, Issue , 2012, Pages 48-60

  Junwal, Mahendra ^a   Sahu, Archana ^a   Handa, Tarun ^a   Shah, Ravi P ^a   Singh, Saranjit ^a  

^a NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH NIPER   (India)

Author keywords

Degradation products; In silico toxicity; LC MS TOF; LC NMR; Oseltamivir phosphate

Indexed keywords

4 ACETAMIDO 5 AMINO 3 (PENTAN 3 YLOXY)CYCLOHEX 1 ENE CARBOXYLIC ACID; 4,5 DIAMINO 3 (PENTAN 3 YLOXY)CYCLOHEX 1 ENE CARBOXYLIC ACID; CARBOXYLIC ACID DERIVATIVE; ETHYL 4,5 DIAMINO 3 (PENTAN 3 YLOXY)CYCLOHEX 1 ENE CARBOXYLATE; OSELTAMIVIR; UNCLASSIFIED DRUG;

ACIDITY; ALKALINITY; ARTICLE; DRUG DEGRADATION; DRUG HYDROLYSIS; DRUG ISOLATION; DRUG PURIFICATION; DRUG STRUCTURE; ISOMER; LIQUID CHROMATOGRAPHY; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; TEMPERATURE STRESS; TIME OF FLIGHT MASS SPECTROMETRY;

ANTIVIRAL AGENTS; CHROMATOGRAPHY, LIQUID; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; OSELTAMIVIR; STRESS, PSYCHOLOGICAL;

EID: 84862798459     PISSN: 07317085     EISSN: 1873264X     Source Type: Journal    
DOI: 10.1016/j.jpba.2012.01.001     Document Type: Article

References (23)

1. Kumar S., Chusid M.J., Willoughby R.E., Havens P.L., Kehl S.C., Ledeboer N.A., Li S.H., Henrickson K.J. Introduction of a novel swine-origin influenza a (H1N1) virus into Milwaukee, Wisconsin in 2009. Viruses 2009, 1:72-83.
2. Li Z.N., Steinhauer D.A. The mechanism and inhibition of influenza virus entry. J. Viral Entry 2006, 2:57-66.
3. Nicholson K.G., Aoki F.Y., Osterhaus A., Trottier S., Carewicz O., Mercier C.H., Rode A., Kinnersley N., Ward P. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Lancet 2000, 355:1845-1850.
4. Available at: (accessed on 25.10.11). http://www.who.int/medicines/areas/quality_safety/quality_assurance/Oseltamivir_shelf-life_QAS11-398_30032011.pdf.
5. Charles J.J., Geneste C., Laborde E.K., Gheyouche R., Boudis H., Dubost J.P. Development and validation of a rapid HPLC method for the determination of oseltamivir phosphate in Tamiflu and generic versions. J. Pharm. Biomed. Anal. 2008, 44:1008-1013.
6. Narasimhan B., Abida K., Srinivas K. Stability indicating RP-HPLC method development and validation for oseltamivir API. Chem. Pharm. Bull. 2008, 56:413-417.
7. Raghuram P., Soma R.I.V., Reddy R., Sriramulu J. A stability indicating LC method for oseltamivir phosphate. Anal. Chem. 2008, 7:617-624.
8. Oliyai R., Yuan L., Dahl T.C., Swaminathan S., Wang K., Lee W.A. Biexponential decomposition of a neuraminidase inhibitor prodrug (GS-4104) in aqueous solution. Pharm. Res. 1998, 15:1300-1304.
9. Available at: (accessed on 27.06.11). http://www.who.int/medicines/publications/pharmacopoeia/Oseltamivir_monoQAS06_190revised09.pdf.
10. Available at: (accessed on 25.10.11). http://www.usp.org/pdf/EN/USPNF/oseltamivirPhosphateCapsulesA.pdf.
11. ICH Stability testing of new drug substances and products Q1A (R2). International Conference on Harmonisation 2003.
12. ICH Stability testing: photostability testing of new drug substances and products Q1B. International Conference on Harmonisation 1996.
13. Bakshi M., Singh S. Guidance on conduct of stress tests to determine inherent stability of drugs. Pharm. Technol. On-line 2000, 24:1-14.
14. Enslein K., Gombar V.K., Blake B.W. Use of SAR in computer-assisted prediction of carcinogenicity and mutagenicity of chemicals by the TOPKAT program. Mutat. Res. 1994, 305:47-61.
15. Ridings J.E., Barratt M.D., Cary R., Earnshaw C.G., Eggington C.E., Ellis M., Judson P.N., Langowski J.J., Mearchant C.A., Payne M.P., Watson W.P., Yih T.D. Computer prediction of possible toxic action from chemical structure: an update of the DEREK system. Toxicology 1996, 106:267-279.
16. March J. Advanced Organic Chemistry: Reactions, Mechanisms and Structure 2005, John Wiley and Sons, Singapore, p. 384, 885. 4th ed.
17. Pavlova L.V., Rachinskii F.Y. Rearrangements connected with the migration of acyl and certain other groups. Russian Chem. Rev. 1968, 37:587-602.
18. Chung S.K., Chang Y.T. Base-catalyzed acyl migrations in myo-inositol dibenzoates. J Chem. Soc. Chem. Commun. 1995, 13-14.
19. Zamir L.O., Balachandran S., Zheng Y.F., Nedea M.E., Caron G., Nikolakakis A., Vishwakarma R.A., Sauriol F., Mamer O. Acid catalyzed rearrangement and acyl migration studies on 9-dihydro-13-aceylbaccatin-lll, a major taxane from taxus canadensis. Tetrahedron 1997, 53:15991-16008.
20. Müller L., Mauthe R.J., Riley C.M., Andino M.M., Antonis D.D., Beels C., DeGeorge J., De Knaep A.G.M., Ellison D., Fagerland J.A., Frank R., Fritschel B., Galloway S., Harpur E., Humfrey C.D.N., Jacks A.S., Jagota N., Mackinnon J., Mohan G., Ness D.K., O'Donovan M.R., Smith M.D., Vudathala G., Yotti L. A rationale for determining, testing, and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity. Regul. Toxicol. Pharm. 2006, 44:198-211.
21. (accessed on 25.10.11). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discus%20ssion/human/000402/WC500033103.pdf.
22. He G., Massarella J., Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite R 64-0802. Clin. Pharmacokinet. 1999, 37:471-484.
23. ICH Impurities in new drug substances, Q3A (R2). International Conference on Harmonisation 2006.