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

Danafar, Hossein; Hamidi, Mehrdad

doi:10.17795/jjnpp-36758

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…29 However, the clinical application of this drug is limited by its toxic dose-related side effects and drug resistance by target cells. 30 Therefore, MTX should be protected from chemical damage prior to its application in cancer therapy. Therefore, in this study we want to reduce the side effects of MTX and increase its effectiveness on cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells

et al. 2017

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Methotrexate is one of the most effective drugs that is commonly used in the treatment of cancer. However, its application is limited due to low solubility, high toxicity and rapid metabolism. Therefore, in the present study, worm-like polymeric nanoparticles as carrier of methotrexate were prepared using biodegradable copolymers (mPEG-PCL). The impact of nanoparticles' geometry on the loading, delivery and drug's anti-cancer activity was investigated. The di-block copolymer mPEG-PCL was being synthesized by a ring opening polymerization of ɛ-caprolactone in the presence of mPEG as the initiator and Sn(oct) as the catalyst. It was used for the preparation of worm-like micelles and coated with silica, so that their structures are stable after drying. The synthesized copolymers and nanoparticles were characterized by FTIR, HNMR, GPC, XRD, TGA, DLS, and FE-SEM analyses. The efficiencies of drug loading and release of nanoparticles as in vitro, was studied by high performance liquid chromatography. The MTT method was used to estimate the toxicity on MCF-7 cell category. The obtained results showed that the nanoparticles were worm-like particles with less than 150 nm diameter and about 1 µm length. The loading and encapsulation efficiencies of drug by the worm-like nanoparticles were 3.5 ± 0.14% and 65.6 ± 0.12%, respectively, while they were obtained as 2.1 ± 0.08% and 26 ± 0.10%, respectively, for spherical nanoparticles. The methotrexate diffusional behavior of worm-like nanoparticles was compared with that of the spherical ones. On the other hand, the anti-cancer activity of MTX-loaded nanoparticles was more than the free drug. The results of the MTT assay showed strong and dose-dependent inhibition of cell (MCF-7 category) growth by the nanoparticles compared with MTX. The inhibitory concentrations (IC i.e. reduction viability of cell to 50%) obtained for worm-like, spherical nanoparticles and free drug (incubation times 72 h) were 8.25 ± 0.20, 9.15 ± 0.17, 12.28 ± 0.15 µg/mL, respectively. It can be concluded that application of non-spherical nanoparticles is a better and more effective strategy for controlled and slow release of methotrexate in the treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

“…MTX is used in the treatment of breast, head and nose, lungs and Non-Hodgkin Lymphoma cancers. [29][30][31] However, the wide use of this drug is still limited due to its toxicity and side effects. In addition, the variability and unpredictability of the function of drug causes the treatment failure.…”

Section: Introductionmentioning

confidence: 99%

Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells

et al. 2017

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“…Methotrexate (MTX), also known as amethopterin, is a folic acid antagonist widely used as a chemotherapy agent for treating different types of cancer such as breast cancer, leukemia, lung cancer, lymphoma, and osteosarcoma; also for treatment of autoimmune diseases such as psoriasis, rheumatoid arthritis, and Crohn′s disease . The action mechanism of MTX is based on inhibition of dihydrofolate reductase (DHFR) enzyme, which participates in the tetrahydrofolate synthesis that is necessary for building the cell′s DNA, thus MTX inhibits the building of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Monitoring of Methotrexate Anticancer Drug in Human Blood Serum by Using in situ Solvothermal Synthesized Fe₃O₄/ITO Electrode

et al. 2019

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Here, we reported on a one‐step fabrication of magnetite Fe3O4 nanoparticles/indium tin oxide (ITO) electrode based on the direct growing of Fe3O4 nanoparticles on the ITO surface by using a solvothermal process. The modified electrode was used as electrochemical methotrexate (MTX) biosensor with high sensitivity based on cyclic voltammetry and square wave voltammetry techniques. The results demonstrated a linear relationship between the MTX concentration and its oxidation current peak over a wide range from 10−5 to 10−14 mole/L with a limit of detection of 0.4×10−15 M based on the square wave voltammetry (SWV) technique. In addition, Fe3O4/ITO electrode showed a good capability for measuring very low concentrations of MTX drug dissolved in human serum solution. Also, Fe3O4/ITO electrode was used for detecting MTX in blood serum samples collected from patients after their treatment with MTX. The prepared electrode showed the higher sensitivity that higher than the Viva‐E instrument, which opens the door for developing a cheap, simple and higher sensitive MTX sensor.

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“…Typically, in LDMTX (a) per os or subcutaneous routes are used, administration is once a week and the steady state is obtained after 6 months of treatment; in HDMTX (Grim et al, ) (b), the intravenous route is the most used and, consequently, systemic doses are high and steady state is more quickly achieved (Danafar & Hamidi, ; Holmboe, Andersen, Morkrid, Slordal, & Hall, ).…”

Section: Introductionmentioning

confidence: 99%

Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review

Silva

Ribeiro

Gonçalves

et al. 2018

Biomedical Chromatography

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Methotrexate (MTX) is an antifolate drug used for several diseases. Depending on the disease, MTX can be administered at low dose (LDMTX) in some autoimmune diseases, like rheumatoid arthritis, or at high dose (HDMTX) in some cancers, such as acute lymphoblastic leukemia. After absorption, MTX is metabolized in the liver to 7-hydroxymethotrexate and in the intestine to 2,4-diamino-N10-methylpteroic acid (DAMPA). Moreover, inside red blood cells, MTX is converted to active metabolites, MTX polyglutamates (MTXPGs), contributing to its pharmacodynamics. Owing to its narrow therapeutic range, and inter- and intra-patient variability, either noneffectiveness and/or toxicity may occur. Because of the existence of a relationship between drug therapeutic outcome and its systemic concentration, therapeutic drug monitoring (TDM) may ensure the effectiveness and safety of MTX use. In order to monitor the optimization of patient clinical response profile, several analytical methods have been described for TDM in biological samples. These include liquid chromatography (LC) coupled with ultraviolet detection, fluorescence detection or mass spectrometry, each one presenting advantages and drawbacks. This paper reviews the most commonly used techniques for sample preparation and critically discusses the current LC methods applied for the TDM of MTX in biological samples, at LDMTX and HDMTX.

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

Cited by 6 publications

References 24 publications

Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells

Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells

Electrochemical Monitoring of Methotrexate Anticancer Drug in Human Blood Serum by Using in situ Solvothermal Synthesized Fe₃O₄/ITO Electrode

Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review

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

Cited by 6 publications

References 24 publications

Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells

Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells

Electrochemical Monitoring of Methotrexate Anticancer Drug in Human Blood Serum by Using in situ Solvothermal Synthesized Fe3O4/ITO Electrode

Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review

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Electrochemical Monitoring of Methotrexate Anticancer Drug in Human Blood Serum by Using in situ Solvothermal Synthesized Fe₃O₄/ITO Electrode