Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

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

Back
Research Article

Development and Validation of an LC-MS/MS Method for Quantitative Determination of EAI045, A Novel EGFR Inhibitor, in Rat Plasma

Author(s): Zixuan Chu, Mingxing Xue and Shan Xiong*

Volume 16, Issue 3, 2020

Page: [273 - 279] Pages: 7

DOI: 10.2174/1573412915666190206125557

Price: $65

Abstract

Background: EAI045 is the fourth-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), which can overcome acquired resistance to the third-generation EGFR TKIs and is the first allosteric inhibitor that targets T790M and C797S EGFR mutants.

Methods: A rapid and sensitive LC-MS/MS method was established and validated for the quantification of EAI045 in rat plasma. Chromatographic separation was carried out at 25°C on a Hypersil GOLD C18 column (50 mm × 2.1 mm, 3 μm) and eluted on a gradient mobile phase of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.5 mL/min. The mass spectrometer was operated in the positive ESI mode and selected reaction monitoring mode.

Results: The assay was validated over a concentration range of 1.0 - 1000 ng/mL for EAI045 with a lower limit of quantification (LLOQ) of 1.0 ng/mL. The intra- and inter-batch accuracy for the EAI045 ranged from 92.25% to 97.18% and 95.94% to 102.69%, and the intra- and inter-batch precision for the EAI045 ranged from 1.41% to 4.57% and 5.18% to 6.37%, respectively. The extraction recovery, matrix effect and stability met all requirements of the guidelines for bioanalytical method validation.

Conclusion: The rapid and sensitive LC-MS/MS method was successfully applied in a pharmacokinetic study of EAI045 following oral administration (5 mg/kg) to rats.

Keywords: EAI045, cancer, epidermal growth factor receptor tyrosine kinase inhibitor, LC-MS/MS, pharmacokinetic study, rat.

« Previous Next »
Graphical Abstract

[1]
Chan, B.A.; Hughes, B.G. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl. Lung Cancer Res., 2015, 4(1), 36-54.
[PMID: 25806345]
[2]
Chan, B.A.; Coward, J.I. Chemotherapy advances in small-cell lung cancer. J. Thorac. Dis., 2013, 5(Suppl. 5), S565-S578.
[PMID: 24163749]
[3]
Arteaga, C.L. The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. J. Clin. Oncol., 2001, 19(18)(Suppl.), 32S-40S.
[PMID: 11560969]
[4]
Yarden, Y.; Sliwkowski, M.X. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell Biol., 2001, 2(2), 127-137.
[http://dx.doi.org/10.1038/35052073] [PMID: 11252954]
[5]
Tan, C.S.; Cho, B.C.; Soo, R.A. Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor -mutant non-small cell lung cancer. Lung Cancer, 2016, 93, 59-68.
[http://dx.doi.org/10.1016/j.lungcan.2016.01.003] [PMID: 26898616]
[6]
Xiong, S.; Deng, Z.; Sun, P.; Mu, Y.; Xue, M. Development and validation of a rapid and sensitive LC-MS/MS method for the pharmacokinetic study of osimertinib in rats. J. AOAC Int., 2017, 100(6), 1771-1775.
[http://dx.doi.org/10.5740/jaoacint.16-0362] [PMID: 28534470]
[7]
Sequist, L.V.; Rolfe, L.; Allen, A.R. Rociletinib in EGFR-mutated non-small-cell lung cancer. N. Engl. J. Med., 2015, 373(6), 578-579.
[http://dx.doi.org/10.1056/NEJMc1506831] [PMID: 26244318]
[8]
Chi, A.; Remick, S.; Tse, W. EGFR inhibition in non-small cell lung cancer: current evidence and future directions. Biomark. Res., 2013, 1(1), 2.
[http://dx.doi.org/10.1186/2050-7771-1-2] [PMID: 24252457]
[9]
Sharma, S.V.; Bell, D.W.; Settleman, J.; Haber, D.A. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer, 2007, 7(3), 169-181.
[http://dx.doi.org/10.1038/nrc2088] [PMID: 17318210]
[10]
Engel, J.; Richters, A.; Getlik, M.; Tomassi, S.; Keul, M.; Termathe, M.; Lategahn, J.; Becker, C.; Mayer-Wrangowski, S.; Grütter, C.; Uhlenbrock, N.; Krüll, J.; Schaumann, N.; Eppmann, S.; Kibies, P.; Hoffgaard, F.; Heil, J.; Menninger, S.; Ortiz-Cuaran, S.; Heuckmann, J.M.; Tinnefeld, V.; Zahedi, R.P.; Sos, M.L.; Schultz-Fademrecht, C.; Thomas, R.K.; Kast, S.M.; Rauh, D. Targeting drug resistance in EGFR with covalent inhibitors: A structure-based design approach. J. Med. Chem., 2015, 58(17), 6844-6863.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01082] [PMID: 26275028]
[11]
Wang, S.; Song, Y.; Liu, D. EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance. Cancer Lett., 2017, 385, 51-54.
[http://dx.doi.org/10.1016/j.canlet.2016.11.008] [PMID: 27840244]
[12]
Wang, S.; Song, Y.; Yan, F.; Liu, D. Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors. Front. Med., 2016, 10(4), 383-388.
[http://dx.doi.org/10.1007/s11684-016-0488-1] [PMID: 27770386]
[13]
Lv, H.; Shen, E.; Luo, L.; Xu, Y.; Pan, Y.; Wu, K.; Xing, Z.; Ye, F.; Zhang, Y. An UPLC-MS/MS method for the determination of EAI045 in plasma and tissues and its application to pharmacokinetic and distribution studies in rats. Pharmazie, 2018, 73(11), 630-634.
[PMID: 30396380]
[14]
US DHHS. FDA; CDER. Guidance for Industry: Bioanalytical Method Validation, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Center for Veterinary Medicine, CMV. 2013.
[15]
Cao, G.Y.; Han, S.Q.; Li, K.K.; Shen, L.; Wang, X.H.; Zhang, Y.B. Pharmacokinetics and tissue distribution study of ferruginol in wistar rat by high-performance liquid chromatography. Curr. Pharm. Anal., 2019, 15, 67-73.
[http://dx.doi.org/10.2174/1573412914666180508154147]
[16]
Sun, J.L.; Xu, W.; Song, J.K.; Li, X.; Guo, Q.; Sun, W.; Han, B.; Du, G.H.; Jing, F.B. A novel UPLC-MS/MS method for the determination of salvianolic acid A in rat urine, feces, and bile and its application to excretion study. Curr. Pharm. Anal., 2018, 14, 1-7.
[17]
Yi, Z.; Ma, L.; Wang, B.; Cai, W.; Xiang, Z. An UPLC method for determination of Geraniin in rat plasma and its application to pharmacokinetic studies. Curr. Pharm. Anal., 2017, 13(4), 398-402.
[http://dx.doi.org/10.2174/1573412912666160527125937] [PMID: 28845150]
[18]
Sun, S.; Zhang, X.; Luo, L.D.; Wang, P.; Bai, M.X.Yu. Jia.; Guo, X.J. Simultaneous determination of kirenol, rosmarinic acid and caffeic acid in rat plasma and pharmacokinetic study after oral administration of the extract of manxingshizhen preparation by UPLC-MS/MS. Curr. Pharm. Anal., 2019, 15, 74-81.
[http://dx.doi.org/10.2174/1573412913666170808100104]

Rights & Permissions Print Cite
Article Metrics
21
3
1
1
© 2024 Bentham Science Publishers | Privacy Policy