Jundishapur Journal of Natural Pharmaceutical Products

Published by: Kowsar

Pharmacokinetics and Bioequivalence of Methotrexate in Human Plasma Studied by Liquid Chromatography-Mass Spectrometry (LC-MS)

Hossein Danafar 1 , 2 , * and Mehrdad Hamidi 3
Authors Information
1 Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, IR Iran
2 Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IR Iran
3 Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IR Iran
Article information
  • Jundishapur Journal of Natural Pharmaceutical Products: May 01, 2016, 11 (2); e36758
  • Published Online: May 21, 2016
  • Article Type: Research Article
  • Received: February 3, 2016
  • Revised: February 27, 2016
  • Accepted: March 16, 2016
  • DOI: 10.17795/jjnpp-36758

To Cite: Danafar H, Hamidi M. Pharmacokinetics and Bioequivalence of Methotrexate in Human Plasma Studied by Liquid Chromatography-Mass Spectrometry (LC-MS), Jundishapur J Nat Pharm Prod. 2016 ; 11(2):e36758. doi: 10.17795/jjnpp-36758.

Copyright © 2016, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Materials and Methods
4. Results
5. Discussion
  • 1. Csordas K, Hegyi M, Eipel OT, Muller J, Erdelyi DJ, Kovacs GT. Comparison of pharmacokinetics and toxicity after high-dose methotrexate treatments in children with acute lymphoblastic leukemia. Anticancer Drugs. 2013; 24(2): 189-97[DOI][PubMed]
  • 2. Shah GD, DeAngelis LM. Treatment of primary central nervous system lymphoma. Hematol Oncol Clin North Am. 2005; 19(4): 611-27[DOI][PubMed]
  • 3. Widemann BC, Adamson PC. Understanding and managing methotrexate nephrotoxicity. Oncologist. 2006; 11(6): 694-703[DOI][PubMed]
  • 4. Lin F, Yue J, Tang LN, Yao Y. Monitoring the plasma concentration of high dosage of methotrexate during chemotheraphy for osteosarcoma and its clinical significance. Tumor. 2008; 28(5): 440-2
  • 5. Volk EL, Rohde K, Rhee M, McGuire JJ, Doyle LA, Ross DD, et al. Methotrexate cross-resistance in a mitoxantrone-selected multidrug-resistant MCF7 breast cancer cell line is attributable to enhanced energy-dependent drug efflux. Cancer Res. 2000; 60(13): 3514-21[PubMed]
  • 6. Loscher W, Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx. 2005; 2(1): 86-98[DOI][PubMed]
  • 7. Begley DJ. ABC transporters and the blood-brain barrier. Curr Pharm Des. 2004; 10(12): 1295-312[PubMed]
  • 8. Kruh GD, Zeng H, Rea PA, Liu G, Chen ZS, Lee K, et al. MRP subfamily transporters and resistance to anticancer agents. J Bioenerg Biomembr. 2001; 33(6): 493-501[PubMed]
  • 9. Danafar H, Hamidi M. LC-MS Method for Studying the Pharmacokinetics and Bioequivalence of Clonidine Hydrochloride in Healthy Male Volunteers. Avicenna J Med Biotechnol. 2016; 8(2): 91-8[PubMed]
  • 10. Li H, Luo W, Zeng Q, Lin Z, Luo H, Zhang Y. Method for the determination of blood methotrexate by high performance liquid chromatography with online post-column electrochemical oxidation and fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 845(1): 164-8[DOI][PubMed]
  • 11. Li C, Zhao X, Wang Y, Yang H, Li H, Li H, et al. Prolongation of time interval between doses could eliminate accelerated blood clearance phenomenon induced by pegylated liposomal topotecan. Int J Pharm. 2013; 443(1-2): 17-25[DOI][PubMed]
  • 12. Ma J, Ping YD, Zhu XQ, Li Q. HPLC determination of methotrexate in human plasma and its clinical application. Chinese Remedies Clin. 2011; 11(8): 916-7
  • 13. Uchiyama M, Matsumoto T, Matsumoto T, Jimi S, Takamatsu Y, Tamura K, et al. Simple and sensitive HPLC method for the fluorometric determination of methotrexate and its major metabolites in human plasma by post-column photochemical reaction. Biomed Chromatogr. 2012; 26(1): 76-80[DOI][PubMed]
  • 14. Bouquie R, Deslandes G, Bernáldez BN, Renaud C, Dailly E, Jolliet P. A fast LC-MS/MS assay for methotrexate monitoring in plasma: validation, comparison to FPIA and application in the setting of carboxypeptidase therapy. Analytic Methods. 2014; 6(1): 178-86
  • 15. Danafar H, Hamidi, M. . Liquid chromatography–tandem mass spectrometry (LC-MS) method for the assignment of enalapril and enalaprilat in human plasma. Pharm Biomed Res. 2015; 1(3): 47-58
  • 16. Sonemoto E, Kono N, Ikeda R, Wada M, Ueki Y, Nakashima K. Practical determination of methotrexate in serum of rheumatic patients by LC-MS/MS. Biomed Chromatogr. 2012; 26(11): 1297-300[DOI][PubMed]
  • 17. Thappali SR, Varanasi KV, Veeraraghavan S, Vakkalanka SK, Khagga M. Simultaneous determination of methotrexate, dasatinib and its active metabolite N- deshydroxyethyl dasatinib in rat plasma by LC-MS/MS: method validation and application to pharmacokinetic study. Arzneimittelforschung. 2012; 62(12): 624-30[DOI][PubMed]
  • 18. Rule G, Chapple M, Henion J. A 384-well solid-phase extraction for LC/MS/MS determination of methotrexate and its 7-hydroxy metabolite in human urine and plasma. Anal Chem. 2001; 73(3): 439-43[PubMed]
  • 19. Danafar H, Hamidi M. Simple and Sensitive High-Performance Liquid Chromatography (HPLC) Method with UV Detection for Mycophenolic Acid Assay in Human Plasma. Application to a Bioequivalence Study. Adv Pharm Bull. 2015; 5(4): 563-8[DOI][PubMed]
  • 20. Danafar, H. , Hamidi M. Simple and sensitive high performance liquid chromatographic method for the simultaneous quantitation of the phenylalanine in human plasma. Pharm Biomed Res. 2015; 1(3): 11-9
  • 21. Danafar H, Hamidi M. Pharmacokinetics and Bioequivalence Study of Amlodipine and Atorvastatin in Healthy Male Volunteers by LC-MS. Pharm Sci. 2015; 21(3)
  • 22. Danafar H. Method validation of clonidine hydrochloride in human plasma by LC-MS technique. Pharm Biomed Res. 2015; 1(4): 48-58
  • 23. Guidance for Analytical Procedures and Methods Validation for Drugs and Biologics Guidance for Industry. 2015;
  • 24. Chorilli M, Bonfilio R, Louvandini CR, Salgado HR. Development and Validation of an LC-MS/MS Method for Quantitative Analysis of Mirtazapine in Human Plasma. Am J Analytic Chem. 2011; 2(6): 650
  • 25. Danafar H, Hamidi M. A Rapid and Sensitive LC–MS Method for Determination of Ezetimibe Concentration in Human Plasma: Application to a Bioequivalence Study. Chromatographia. 2013; 76(23-24): 1667-75
  • 26. Mitchell BL, Yasui Y, Li CI, Fitzpatrick AL, Lampe PD. Impact of freeze-thaw cycles and storage time on plasma samples used in mass spectrometry based biomarker discovery projects. Cancer Inform. 2005; 1: 98-104[PubMed]
  • 27. Cuhadar S, Koseoglu M, Atay A, Dirican A. The effect of storage time and freeze-thaw cycles on the stability of serum samples. Biochem Med (Zagreb). 2013; 23(1): 70-7[PubMed]
  • 28. Boroujerdi M. Pharmacokinetics: principles and applications. 2001;
  • 29. Guidance for industry, bioavailability and bioequivalence studies for orally administered drug products; General considerations. 2002;
  • 30. Asiri YA, Al-Said MS, Al-Khamis KI, Niazy EM, El-Sayed YM, Al-Rashood KA, et al. Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers. Int J Clin Pharmacol Ther. 2005; 43(10): 499-504[PubMed]
  • 31. Schall R, Luus HG. Comparison of absorption rates in bioequivalence studies of immediate release drug formulations. Int J Clin Pharmacol Ther Toxicol. 1992; 30(5): 153-9[PubMed]
  • 32. Seideman P, Beck O, Eksborg S, Wennberg M. The pharmacokinetics of methotrexate and its 7-hydroxy metabolite in patients with rheumatoid arthritis. Br J Clin Pharmacol. 1993; 35(4): 409-12[PubMed]
  • 33. Koufopantelis P, Georgakakou S, Kazanis M, Giaginis C, Margeli A, Papargiri S, et al. Direct injection liquid chromatography/positive ion electrospray ionization mass spectrometric quantification of methotrexate, folinic acid, folic acid and ondansetron in human serum. J Chromatogr B Analyt Technol Biomed Life Sci. 2009; 877(30): 3850-6[DOI][PubMed]
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .
Readers' Comments