Identification and characterization of geometrical isomeric photo degradation product of eprosartan using LC-MS and LC-NMR

Ravi Piyushkumar Shah, Archana Sahu, Saranjit Singh

Abstract


The degradation of eprosartan was evaluated under ICH/WHO prescribed stress conditions. The drug degraded to only one product under photo alkali condition, whereas it was stable to conditions of hydrolysis, oxidation and thermal stress. The drug and its co-eluting product were well separated on RP-HPLC in a gradient mode. Subsequently, LC-MS/TOF and on-line H/D exchange studies were performed on both of them. The two showed same molecular mass, similar fragment ions and even the same number of labile hydrogens indicating the product to be an isomer of the drug. To confirm the same, 1H and COSY LC-NMR studies were carried out by using an enriched sample. Distinguishing behaviour of chemical shifts proved the product to be (Z)-4-((2-butyl-5-(2-carboxy-3-(thiophen-2-yl)prop-1-enyl)-1H-imidazol-1-yl)methyl)benzoic acid. The structure was further supported by differential LC-MS ion intensities of the drug and the product.2_2_152_157_800

Keyword(s)


Eprosartan; Degradation behaviour; Photoisomerization; Geometric isomer; LC-MS; LC-NMR

European Journal of Chemistry, 2 (2), (2011), 152-157

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DOI: http://dx.doi.org/10.5155/eurjchem.2.2.152-157.170

 

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References

[1]. ICH Topic Q1A (R2), Stability Testing of New Drug Substances and Products, in: International Conference on Harmonisation, IFPMA, Geneva, 2003.

[2]. WHO, Draft Stability Testing of Active Pharmaceutical Ingredients and Pharmaceutical Products, World Health Organization, Geneva, 2007.

[3]. Murakami, T.; Kawasaki, T.; Takemura, A.; Fukutsu, N.; Kishi, N.; Kusu, F. J. Chromatogr. A 2008, 1208, 164-174.
doi:10.1016/j.chroma.2008.08.076
PMid:18778828

[4]. Shah, R. P.; Kumar, V.; Singh, S. Rapid Commun. Mass Spectrom. 2008, 22, 613-622.
doi:10.1002/rcm.3403
PMid:18247406

[5]. Novak, P.; Tepes, P.; Ilijas, M.; Fistric, I.; Bratos, I.; Avdagic, A.; Hamersak, Z.; Markovic, V. G.; Dumic, M. J. Pharm. Biomed. Anal. 2009, 50, 68-72.
doi:10.1016/j.jpba.2009.03.017
PMid:19410412

[6]. Dev, R. V.; Kiran, G. S. U.; Subbaiah, B. V.; Babu, B. S.; Babu, J. M.; Dubey, P. K.; Vyas, K. Magn. Reson. Chem. 2009, 47, 443-448.
doi:10.1002/mrc.2404
PMid:19173350

[7]. Shah, R. P.; Sahu, A.; Singh, S. J. Pharm. Biomed. Anal. 2010, 51, 1037-1046.
doi:10.1016/j.jpba.2009.11.008
PMid:20018473

[8]. Shah, R. P.; Singh, S. J. Pharm. Biomed. Anal. 2010, 53, 755-761.
doi:10.1016/j.jpba.2010.05.005
PMid:20554147

[9]. Hoffman, B. B. in: Brunton, L.L. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 11th Edition, McGraw-Hill, 859-860, 2006.

[10]. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?Fuseaction=Search.DrugDetails (accessed on 11 April 2011).

[11]. Hsu, L. C. J. Liq. Chrom. & Rel. Technol. 1998, 21, 1685-1700.
doi:10.1080/10826079808001252
PMCid:1176066

[12]. Xue-Ning, L.; Hong-Rong, X.; Wei-Li, C.; Gang-Yi, L.; Nan-Nan. C.; Chen Y. J. Chromatogr. B 2007, 853, 47-53.

[13]. Ferreirós, N.; Iriarte, G.; Alonsoa, R. M.; Jiménez, R. M.; Ortíz, E. J. Chromatogr. A 2006, 1119, 309-314.
doi:10.1016/j.chroma.2006.02.055
PMid:16542666

[14]. ICH Topic Q1B, Stability Testing: Photostability Testing of New Drug Substances and Products, in: International Conference on Harmonisation, IFPMA, Geneva, 1996.

[15]. Bakshi, M.; Singh, S. J. Pharm. Biomed. Anal. 2002, 28, 1011-1040.
doi:10.1016/S0731-7085(02)00047-X

[16]. Mayer-Helm, B.; Hofbauer, L.; Pani, J. J. Mass. Spectrom. 2010, (Article in Press; doi:10.1002/jms.1757).

[17]. Ge, G. B.; Zhang, R.; Ail, C. Z.; He Y. Q.; Zhang Y. Y.; Liu X. B.; Yang L.; Wang Z. T.; Yang L. Rapid Commun. Mass Spectrom. 2009, 23, 425-432.
doi:10.1002/rcm.3892
PMid:19125430

[18]. Brum, J.; Hannah, R. Rapid Commun. Mass Spectrom. 1997, 11, 1430-1434.
doi:10.1002/(SICI)1097-0231(19970830)11:13<1430::AID-RCM7>3.0.CO;2-5

[19]. Thoma, K.; Kuebler, N.; Reimann, E. Pharmazie 1997, 52, 362-373.
PMid:9229718

[20]. Albini, A.; Fasani, E. in: Tønnesen H. H. The Photostability of Drugs and Drug Formulations, 2nd Edition, Taylor and Francis, 69-71, 2004.


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