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Current Pharmaceutical Analysis

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

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Research Article

Determination of Impurities in Perampanel Bulk Drugs by High- Performance Liquid Chromatography and Gas Chromatography

Author(s): Yun-Yan Xia, Qiao-Gen Zou*, Yu-Fei Yang, Qian Sun and Cheng-Qun Han

Volume 17, Issue 7, 2021

Published on: 13 May, 2020

Page: [873 - 884] Pages: 12

DOI: 10.2174/1573412916999200513105657

Price: $65

Abstract

Background: High-Performance Liquid Chromatography (HPLC) method has been used to detect related impurities of perampanel. However, the detection of impurities is incomplete, and the limits of quantification and detection are high. A sensitive, reliable method is badly needed to be developed and applied for impurity detection of perampanel bulk drug.

Objective: Methodologies utilising HPLC and Gas Chromatography (GC) were established and validated for quantitative determination of perampanel and its related impurities (a total of 10 impurities including 2 genotoxic impurities).

Methods: The separation was achieved on a Dikma Diamonsil C18 column (250 mm × 4.6 mm, 5 μm) with the mobile phase of 0.01 mol/L potassium dihydrogen phosphate solution (A) and acetonitrile (B) in gradient elution mode. The compound 2-bromopropane was determined on an Agilent DB-624 column (0.32 mm × 30 m, 1.8 μm) by electron capture detector (μ-ECD) with split injection ratio of 1:5 and proper gradient temperature program.

Results: Both HPLC and GC methods were established and validated to be sensitive, accurate and robust according to the International Council for Harmonization (ICH) guidelines. The methods developed were linear in the selected concentration range (R2≥0.9944). The average recovery of all impurities was between 92.6% and 103.3%. The possible production mechanism of impurities during the synthesis and degradation processes of perampanel bulk drug was also discussed. Five impurities were analyzed by liquid chromatography–mass spectrometry (LC-MS). Moreover, two of them were simultaneously characterized by LC-MS, IR and NMR.

Conclusion: The HPLC and GC methods were developed and optimized, which could be applied for quantitative detection of the impurities, and further stability study of perampanel.

Keywords: Perampanel, impurities, qualitative and quantitative analysis, HPLC, GC, LC-MS.

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[1]
Perucca, E.; French, J.; Bialer, M. Development of new antiepileptic drugs: challenges, incentives, and recent advances. Lancet Neurol., 2007, 6(9), 793-804.
[http://dx.doi.org/10.1016/S1474-4422(07)70215-6] [PMID: 17706563]
[2]
Yu, Y.; Nguyen, D.T.; Jiang, J. G protein-coupled receptors in acquired epilepsy: Druggability and translatability. Prog. Neurobiol., 2019, 183(183), 101682.
[http://dx.doi.org/10.1016/j.pneurobio.2019.101682] [PMID: 31454545]
[3]
Satlin, A.; Kramer, L.D.; Laurenza, A. Development of perampanel in epilepsy. Acta Neurol. Scand. Suppl., 2013, 127(197), 3-8.
[http://dx.doi.org/10.1111/ane.12098] [PMID: 23480150]
[4]
Hanada, T.; Hashizume, Y.; Tokuhara, N.; Takenaka, O.; Kohmura, N.; Ogasawara, A.; Hatakeyama, S.; Ohgoh, M.; Ueno, M.; Nishizawa, Y. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia, 2011, 52(7), 1331-1340.
[http://dx.doi.org/10.1111/j.1528-1167.2011.03109.x] [PMID: 21635236]
[5]
Rogawski, M.A.; Hanada, T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol. Scand. Suppl., 2013, 127(197), 19-24.
[http://dx.doi.org/10.1111/ane.12100] [PMID: 23480152]
[6]
Göde, K.; Grossmann, A.; Rösche, J. Successful treatment of epilepsia partialis continua due to Rassmussen encephalitis with perampanel. J. Epileptol., 2016, 24(1), 67-70.
[http://dx.doi.org/10.1515/joepi-2016-0003]
[7]
Mohammad, H.; Sekar, S.; Wei, Z.; Moien-Afshari, F.; Taghibiglou, C. Perampanel but not amantadine prevents behavioral alterations and epileptogenesis in pilocarpine rat model of status epilepticus. Mol. Neurobiol., 2019, 56(4), 2508-2523.
[http://dx.doi.org/10.1007/s12035-018-1230-6] [PMID: 30039334]
[8]
Lange, F.; Weßlau, K.; Porath, K.; Hörnschemeyer, J.; Bergner, C.; Krause, B.J.; Mullins, C.S.; Linnebacher, M.; Köhling, R.; Kirschstein, T. AMPA receptor antagonist perampanel affects glioblastoma cell growth and glutamate release in vitro. PLoS One, 2019, 14(2), e0211644.
[http://dx.doi.org/10.1371/journal.pone.0211644] [PMID: 30716120]
[9]
Inami, H.; Shishikura, J.I.; Yasunaga, T.; Hirano, M.; Kimura, T.; Yamashita, H.; Ohno, K.; Sakamoto, S. Synthesis and Pharmacological Evaluation of 3-[(4-Oxo-4H-pyrido[3,2-e][1,3]thiazin-2-yl)(phenyl)amino]propanenitrile Derivatives as Orally Active AMPA Receptor Antagonists. Chem. Pharm. Bull. (Tokyo), 2019, 67(7), 699-706.
[http://dx.doi.org/10.1248/cpb.c18-00977] [PMID: 31257325]
[10]
Rohracher, A.; Kalss, G.; Neuray, C.; Höfler, J.; Dobesberger, J.; Kuchukhidze, G.; Kreidenhuber, R.; Florea, C.; Thomschewski, A.; Novak, H.F.; Pilz, G.; Leitinger, M.; Trinka, E. Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit: A single-center audit of 30 patients. Epilepsia, 2018, 59(49)(Suppl. 2), 234-242.
[http://dx.doi.org/10.1111/epi.14494] [PMID: 30043411]
[11]
Mano, Y.; Takenaka, O.; Kusano, K. High-performance liquid chromatography-tandem mass spectrometry method for the determination of perampanel, a novel α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist in human plasma. J. Pharm. Biomed. Anal., 2015, 107, 56-62.
[http://dx.doi.org/10.1016/j.jpba.2014.12.018] [PMID: 25569285]
[12]
Oi, Y.; Kobayashi, K.; Hitomi, T.; Matsumoto, R.; Ikeda, A.; Takahashi, R. [Low-dose perampanel improved cortical myoclonus and basophobia in a patient with Unverricht-Lundborg disease: a case report]. Rinsho Shinkeigaku, 2018, 58(10), 622-625.
[http://dx.doi.org/10.5692/clinicalneurol.cn-001179] [PMID: 30270337]
[13]
Saida, S.J.; Muthuchamy, M.; Kaliyaperumal, M. Isolation and spectral characterization of degradation impurity in perampanel drug substance using UPLC-MS and NMR spectroscopy: validation of assay method by UPLC. Asian J. Chem., 2018, 30(10), 2215-2219.
[http://dx.doi.org/10.14233/ajchem.2018.21405]
[14]
Zhang, H.; Sun, L.; Zou, L.; Hui, W.; Liu, L.; Zou, Q.; Ouyang, P. Identification, characterization and HPLC quantification of process-related impurities in Trelagliptin succinate bulk drug: Six identified as new compounds. J. Pharm. Biomed. Anal., 2016, 128, 18-27.
[http://dx.doi.org/10.1016/j.jpba.2016.04.041] [PMID: 27209451]
[15]
Nikulin, A.V.; Okuneva, M.V.; Goryainov, S.V.; Potanina, O.G. Development and validation of an HPLC-UV method for arbutin determination in bearberry leaves. Pharm. Chem. J., 2019, 53(8), 736-740.
[http://dx.doi.org/10.1007/s11094-019-02071-3]
[16]
Albayrak; Mevlut; Atila; Alptug. Development and validation of novel UPLC-MS/MS method for the analysis of macitentan in pharmaceutical formulations. Curr. Med. Chem., 2019, 15(5), 554-559.
[17]
Lu, G.; Hu, J. Effect of alpha-hydroxy acids on transformation products formation and degradation mechanisms of carbamazepine by UV/H2O2 process. Sci. Total Environ., 2019, 689(689), 70-78.
[http://dx.doi.org/10.1016/j.scitotenv.2019.06.011] [PMID: 31271991]
[18]
Kumar, A.; Devineni, S.R.; Dubey, S.K.; Kumar, P.; Srivastava, V.; Ambulgekar, G.; Jain, M.; Gupta, D.K.; Singh, G.; Kumar, R.; Hiriyanna, S.G.; Kumar, P. Identification, synthesis and structural characterization of process related and degradation impurities of acrivastine and validation of HPLC method. J. Pharm. Biomed. Anal., 2017, 133, 15-26.
[http://dx.doi.org/10.1016/j.jpba.2016.10.015] [PMID: 27969063]
[19]
Sweidan, K.; Elayan, M.; Sabbah, D.; Idrees, G.; Arafat, T. Study of forced degradation behavior of amisulpride by LC-MS and NMR and development of a stability-indicating method. Curr. Med. Chem., 2018, 14(2), 157-165.
[20]
Kroes, R.; Renwick, A. G.; Feron, V.; Galli, C. L.; Gibney, M.; Greim, H. Application of the threshold of toxicological concern (ttc) to the safety evaluation of cosmetic ingredients. Food & Chemical Toxicology., 2007, 45(12), 0-2562.
[21]
Khorol’skii, M.D.; Anan’ina, O.V.; Chaplenko, A.A.; Nedkov, I.V.; Maslennikova, N.V.; Ramenskaya, G.V. Comparison of approaches to determining N-Nitrosodimethylamine impurity in valsartan drug substance By GC-MS methods. Pharm. Chem. J., 2019, 53(21), 766-770.
[http://dx.doi.org/10.1007/s11094-019-02076-y]
[22]
Larissa, S.B.; Pedro, N.S.J.; Isabela, F.B.B. Maximiliano da, S.S.; Vitor, T.; Cassiana, M.; Marcos, A.S.S.; Paulo, R.O. Determination of hydrochlorothiazide and two major degradation products by stability indicating high performance liquid chromatography. Curr. Med. Chem., 2020, 16(2), 176-180.
[23]
Liu, F.X.; Bi, X.H.; Ren, Z.F.; Zhang, G.H.; Wang, X.M.; Peng, P.A.; Sheng, G.Y. Determination of amines associated with particles by gas chromatography-mass spectrometry. Chin. J. Anal. Chem., 2017, 45(4), 477-482.
[http://dx.doi.org/10.1016/S1872-2040(17)61005-3]

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