Forced degradation of fingolimod: effect of co-solvent and characterization of degradation products by UHPLC-Q-TOF-MS/MS and 1H NMR.
作者： Prinesh N Patel , Pradipbhai D Kalariya , S Gananadhamu , R Srinivas , None
DOI: 10.1016/J.JPBA.2015.07.028
关键词:
摘要: Fingolimod (FGL), an immunomodulator drug for treating multiple sclerosis, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis thermal stress, as per International Conference on Harmonization specified conditions. The showed extensive degradation under base hydrolysis, however, it stable all other A total of three products (DPs) were observed. chromatographic separation the its achieved a Fortis C18 (100×2.1mm, 1.7μm) column with mobile phase composed 0.1% formic acid (Solvent A) acetonitrile B) in gradient mode. All DPs identified characterized by liquid chromatography-quadrupole time flight-mass spectrometry (LC-Q-TOF-MS) combination accurate mass measurements. major DP isolated Nuclear Magnetic resonance spectroscopy. This is typical case where used co-solvent stress studies, reacts FGL hydrolytic conditions produce acetylated DPs. Hence, can be suggested that not preferable FGL. developed UHPLC method validated ICH guidelines.
researchgate.net 
sci-hub.se 参考文章(13)
Pharmaceutical stress testing : predicting drug degradation Taylor & Francis. ,(2005) , 10.1201/9780849359194
Saranjit Singh, Tarun Handa, Mallikarjun Narayanam, Archana Sahu, Mahendra Junwal, Ravi P. Shah, A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products Journal of Pharmaceutical and Biomedical Analysis. ,vol. 69, pp. 148- 173 ,(2012) , 10.1016/J.JPBA.2012.03.044
Corinne Emotte, Fany Deglave, Olivier Heudi, Franck Picard, Olivier Kretz, Fast simultaneous quantitative analysis of FTY720 and its metabolite FTY720-P in human blood by on-line solid phase extraction coupled with liquid chromatography–tandem mass spectrometry Journal of Pharmaceutical and Biomedical Analysis. ,vol. 58, pp. 102- 112 ,(2012) , 10.1016/J.JPBA.2011.09.021
N. Ferreirós, S. Labocha, M. Schröder, H.H. Radeke, G. Geisslinger, LC–MS/MS determination of FTY720 and FTY720-phosphate in murine intracellular compartments and human plasma Journal of Chromatography B. ,vol. 887-888, pp. 122- 127 ,(2012) , 10.1016/J.JCHROMB.2012.01.023
Prinesh N. Patel, D. Rajesh Kumar, S. Gananadhamu, R. Srinivas, Characterization of the stress degradation products of tolvaptan by UPLC-Q-TOF-MS/MS RSC Advances. ,vol. 5, pp. 21142- 21152 ,(2015) , 10.1039/C4RA16644B
N. Rajan, K. Anver Basha, Rapid Determination of Fingolimod Hydrochloride-Related Substances and Degradation Products in API and Pharmaceutical Dosage Forms by Use of a Stability-Indicating UPLC Method Chromatographia. ,vol. 77, pp. 1545- 1552 ,(2014) , 10.1007/S10337-014-2751-4
Pradipbhai D Kalariya, MVN Kumar Talluri, Prinesh N Patel, R Srinivas, None, Identification of hydrolytic and isomeric N-oxide degradants of vilazodone by on line LC–ESI–MS/MS and APCI–MS Journal of Pharmaceutical and Biomedical Analysis. ,vol. 102, pp. 353- 365 ,(2015) , 10.1016/J.JPBA.2014.09.033
Ludwig Kappos, Ernst-Wilhelm Radue, Paul O'Connor, Chris Polman, Reinhard Hohlfeld, Peter Calabresi, Krzysztof Selmaj, Catherine Agoropoulou, Malgorzata Leyk, Lixin Zhang-Auberson, Pascale Burtin, None, A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis The New England Journal of Medicine. ,vol. 362, pp. 387- 401 ,(2010) , 10.1056/NEJMOA0909494
Prinesh N Patel, Roshan M Borkar, Pradipbhai D Kalariya, Rahul P Gangwal, Abhay T Sangamwar, Gananadhamu Samanthula, Srinivas Ragampeta, None, Characterization of degradation products of ivabradine by LC-HR-MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H2SO4 acid hydrolysis. Journal of Mass Spectrometry. ,vol. 50, pp. 344- 353 ,(2015) , 10.1002/JMS.3533
M Balaji, V Srinivasarao, K Ramakrishna, KM Apparao, None, Development and validation of simple stability indicating RP-HPLC method for analysis of saxagliptin and its forced degradation impurities in bulk drug and pharmaceutical dosage form. International Journal of Research and Development in Pharmacy and Life Sciences. ,vol. 2014, ,(2014)