Molecular Formula | C20H22N8O5 |
Molar Mass | 454.45 |
Density | 1.4080 (rough estimate) |
Melting Point | 195°C |
Boling Point | 561.26°C (rough estimate) |
Specific Rotation(α) | +17~+24°(D/20℃)(c=1,Na2CO3 soln.)(calculated on the dehydrous basis) |
Flash Point | 11℃ |
Water Solubility | Insoluble. <0.1 g/100 mL at 19 ºC |
Solubility | Easily soluble in dilute alkali, acid or alkali metal carbonate solution, slightly soluble in dilute hydrochloric acid, almost insoluble in water, ethanol, chloroform, ether. |
Appearance | Yellow crystalline powder |
Merck | 14,5985 |
BRN | 70669 |
pKa | pKa 3.04/4.99(H2O,t =25,I=0.0025) (Uncertain) |
Storage Condition | Keep in dark place,Inert atmosphere,Store in freezer, under -20°C |
Stability | Stable, but light sensitive and hygroscopic. Incompatible with strong acids, strong oxidizing agents. Store at -15C or below. |
Sensitive | Light Sensitive & Hygroscopic |
Refractive Index | 1.6910 (estimate) |
MDL | MFCD00064370 |
Physical and Chemical Properties | Orange-yellow crystalline powder. Melting point 185-204 °c. Soluble in dilute alkali, acid or alkali metal carbonate solution, slightly soluble in dilute hydrochloric acid, almost insoluble in water, ethanol, chloroform, ether. |
Use | Antineoplastic agents for acute leukemia, choriocarcinoma, malignant mole and psoriasis |
Risk Codes | R61 - May cause harm to the unborn child R25 - Toxic if swallowed R36/38 - Irritating to eyes and skin. R46 - May cause heritable genetic damage R39/23/24/25 - R23/24/25 - Toxic by inhalation, in contact with skin and if swallowed. R11 - Highly Flammable |
Safety Description | S53 - Avoid exposure - obtain special instructions before use. S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S36/37 - Wear suitable protective clothing and gloves. S45 - In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.) S36/37/39 - Wear suitable protective clothing, gloves and eye/face protection. S36 - Wear suitable protective clothing. S16 - Keep away from sources of ignition. |
UN IDs | UN 2811 6.1/PG 3 |
WGK Germany | 3 |
RTECS | MA1225000 |
FLUKA BRAND F CODES | 3-8-10 |
TSCA | Yes |
HS Code | 29335995 |
Hazard Class | 6.1(b) |
Packing Group | III |
Toxicity | LD50 oral in rat: 135mg/kg |
Reference Show more | 1. Wang Jingxia, Liu Chunfang, Li Yiqun, etc. Inhibitory effect of Tripterygium wilfordii polyglycoside on angiogenesis in experimental rheumatoid arthritis. Chinese Journal of Traditional Chinese Medicine. 2. Liu Chunfang, Wang Jingxia, He Lianhua, etc. Effect of Fengshi qutong capsule on angiogenesis of synovium in rats with collagen-induced arthritis [J]. Chinese Journal of Traditional Chinese Medicine, 2019, 044(007):1457-1463. 3. Wang Jingxia, Liu Chunfang, He Lianhua, et al. Effect of Fengshi qutong capsule on collagen-induced arthritis in rats [J]. Chinese Journal of Experimental prescriptions, 2019, 25(02):89-95. 4. Liu Chunfang, He Lianhua, Wang Jingxia, et al. Effect of Fengshi qutong capsule on Akt and MAPK signaling pathway in rheumatoid arthritis synovium [J]. Chinese Journal of Experimental prescriptions, 2019, 25(13):43-48. 5. Duan Ziyu, Li Jianguo, Chen Jing, Liu Hongwei, Li Lina, Zhou Wu, Zhang Shoumin. Effect of Liangxue Xiaoyin granules on axis miR-155/SOCS1 in transgenic mice model of psoriasis [J]. Tianjin Medical Journal, 2020,48(11):1045-1049. 6. Ren Zeyu, Jiang Hong, Xu Yan, Shi Yongfang. Preparation and in vitro release of methotrexate loaded PLGA microspheres [J]. Journal of Shihezi University (Natural Science Edition),2020,38(06):767-772. 7. Li Bing-Tong. Effect and mechanism of iguratimod on citrullination of peripheral blood leukocytes in patients with rheumatoid arthritis [J]. Jilin University, 2020. 8. Wang, Kejia, Chunhong Xie, and Daorong Chen. "Flap endonuclease 1 is a promising candidate biomarker in gastric cancer and is involved in cell proliferation and apoptosis." International journal of molecular medicine 33.5 (2014): 1268-1274. https://doi.org 9. Mu, Y. R. , et al. "Acetazolamide ameliorates the severity of collagen-induced arthritis in rats: Involvement of inducing synovial apoptosis and inhibiting Wnt/β-catenin pathway ." International Immunopharmacology 90(2021):107214. 10. Li, Xiangyu, et al. "Folate receptor-targeting mesoporous silica-coated gold nanorod nanoparticles for the synergistic photothermal therapy and chemotherapy of rheumatoid arthritis." RSC Advances 11.6 (2021): 3567-3574.https://doi.org/10.1039/D0RA08689D 11. [IF=4.471] Jinlong Zhao et al."Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis."Int J Nanomed. 2017; 12: 6735-6746 12. [IF=4.421] Fei Hao et al."Targeted Co-Delivery of siRNA and Methotrexate for Tumor Therapy via Mixed Micelles."Pharmaceutics. 2019 Feb;11(2):92 13. [IF=4.101] Kejia Wang et al."Flap endonuclease 1 is a promising candidate biomarker in gastric cancer and is involved in cell proliferation and apoptosis."Int J Mol Med. 2014 May;33(5):1268-1274 14. [IF=3.329] Chengcheng Zou et al."Functional analysis of miR-181a and Fas involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis."Exp Cell Res. 2015 Feb;331:352 15. [IF=2.69] Juan Wu et al."Facile synthesis of magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan hydrogel as MTX carriers for controlled drug release."J Biomat Sci-Polym E. 2016;27(15):1553-1568 16. [IF=2.496] Jiang Wei et al."Synthesis and characterization of magnetic mesoporous core-shell nanocomposites for targeted drug delivery applications."J Porous Mat. 2017 Feb;24(1):257-265 17. [IF=7.727] Lina Guo et al."Rational design of metal-organic frameworks to deliver methotrexate for targeted rheumatoid arthritis therapy."J Control Release. 2021 Feb;330:119 18. [IF=5.455] He Lianhua et al."Shikonin attenuates rheumatoid arthritis by targeting SOCS1/JAK/STAT signaling pathway of fibroblast like synoviocytes."Chin Med-Uk. 2021 Dec;16(1):1-15 19. [IF=5.34] Li Cai et al."7-Hydroxycoumarin mitigates the severity of collagen-induced arthritis in rats by inhibiting proliferation and inducing apoptosis of fibroblast-like synoviocytes via suppression of Wnt/β-catenin signaling pathway."Phytomedicine. 2022 Jan;94: 20. [IF=3.943] Yu-rong Mu et al."Acetazolamide ameliorates the severity of collagen-induced arthritis in rats: Involvement of inducing synovial apoptosis and inhibiting Wnt/β-catenin pathway."Int Immunopharmacol. 2021 Jan;90:107214 21. [IF=3.361] Xiangyu Li et al."Folate receptor-targeting mesoporous silica-coated gold nanorod nanoparticles for the synergistic photothermal therapy and chemotherapy of rheumatoid arthritis."Rsc Adv. 2021 Jan;11(6):3567-3574 22. [IF=2.589] Shenghui Zhong et al."Hyaluronic Acid-Coated MTX-PEI Nanoparticles for Targeted Rheumatoid Arthritis Therapy."Crystals. 2021 Apr;11(4):321 23. [IF=4.932] Bo Meng et al."AMSP-30 m as a novel HIF-1α inhibitor attenuates the development and severity of adjuvant-induced arthritis in rats: Impacts on synovial apoptosis, synovial angiogenesis and sonic hedgehog signaling pathway."Int Immunopharmacol. 2022 Feb;10 24. [IF=3.846] Shichao Wu et al."Methotrexate and 10-hydroxycamptothecine loaded pullulan nanoparticles with the targeting property for efficient cancer therapy."MATERIALS TECHNOLOGY |
This product is a mixture of 4-amino -10-methyl folic acid and structural analogs, the main component is L-( + )-N-[4-[(2, 4-diamino-6-pteridinyl) methyl] methylamino] benzoyl] glutamic acid. The content of C20H22N305 shall be between 98.0% and 102.0% based on the anhydrous content.
take this product, precision weighing, add 0.05mol/L sodium carbonate solution to dissolve and quantitatively dilute to make a solution containing about 10 mg per 1 ml, the specific rotation is 19 ° to 24 ° as determined by law using a 2dm measuring tube (General rule 0621).
take this product, add mobile phase to dissolve and dilute to make a solution containing about 0.2mg per 1ml as a test solution; Take 1ml for precision measurement and put it in a 100ml measuring flask, dilute to the scale with the mobile phase, shake, and serve as a control solution. According to the high performance liquid chromatography (General 0512) test, using bovine serum albumin bonded silica gel as filler, with N-propanol-phosphate buffer (pH 6.9) (0.71% anhydrous disodium hydrogen phosphate solution, add 0.69% sodium dihydrogen phosphate solution 600ml, shake, adjust pH 6.9 with 2mol/L sodium hydroxide solution)(8:92) as mobile phase, the detection wavelength is 302nm. Methotrexate was removed, and the mobile phase was dissolved and diluted to make a solution containing about 40ug per 1ml as a system-suitable solution. 20u1 injection liquid chromatograph, the peak order is (S)-methotrexate peak and (J) -methotrexate peak, the separation degree should be greater than 3.0. 2 ou1 of the test solution and the control solution were respectively injected into the liquid chromatograph, and the chromatograms were recorded. If (K) -methotrexate peak is present in the chromatogram of the test solution, the peak area shall not be greater than 3 times (3.0%) of the main peak area of the control solution.
take this product, add mobile phase to dissolve and dilute to make a solution containing lmg per lml as a test solution; Take 1ml for precision measurement and put it in a 200ml measuring flask, dilute to the scale with the mobile phase, shake, and serve as a control solution. According to the chromatographic conditions under the content determination item, 50 u1 of the test solution and 50 u1 of the control solution are accurately measured and injected into the human liquid chromatograph respectively, and the chromatogram is recorded to 4 times of the retention time of the main component peak. If there are impurity peaks in the chromatogram of the test solution, the peak area of a single impurity shall not be greater than the main peak area of the control solution (0.5%), the sum of each impurity peak area shall not be greater than 4 times (2.0%) of the main peak area of the control solution.
take this product, according to the moisture determination method (General 0832 first method 1), the water content shall not exceed 12.0%.
take l.Og of this product and check it according to law (General rule 0841). The residue left shall not exceed 0.1%.
take 0.5g of this product, add 25% magnesium sulfate sulfuric acid solution (take magnesium sulfate 25g, add 1 mol/ L sulfuric acid solution to dissolve) 4ml, shake, put on water bath and evaporate to dryness, at 800 ° C, it shall be slowly baked until it is completely charring, and the burning time shall not exceed 2 hours. It shall be allowed to cool and inspected according to law (General Principles 0821, second law), and the content of heavy metals shall not exceed 50 parts per million.
measured by high performance liquid chromatography (General 0512).
silica gel bonded with eighteen alkyl silane as filler; Acetonitrile-7.0% citric acid solution-2.0% anhydrous disodium hydrogen phosphate solution (8.5:10:80) (7.0% citric acid solution or 2.0% disodium hydrogen phosphate solution to adjust the pH value to 6.0) as the mobile phase; The detection wavelength was 302nm. Methotrexate and folic acid were taken, dissolved and diluted with the mobile phase to prepare about 0 per 1 ml. lmg mixed solution, take 10ul injection human liquid chromatograph, record chromatogram, the number of theoretical plate according to methotrexate peak calculation is not less than 1000, the separation degree of methotrexate peak and folic acid peak should be greater than 8.0.
take this product, precision weighing, adding mobile phase dissolution and quantitative dilution to make a solution containing about 0.lm g per lml, take 10ul injection liquid chromatography with precision, record chromatogram; in addition, the methotrexate reference substance was determined by the same method, and the peak area was calculated by the external standard method.
antineoplastic agents.
shade, seal, and store in a cool place.
This product contains methotrexate (C20H22N805) should be 95.0% to 110.0% of the label.
This product is light orange and yellow.
Take 10 tablets of this product, precision weighing, fine grinding, precision weighing appropriate amount (about equivalent to methotrexate 2.5mg), put it in a 25ml measuring flask, add mobile phase 20ml, ultrasonic dissolution of methotrexate, cool, dilute to the scale with mobile phase, shake well, filter, take the filtrate as the test solution, according to the method under methotrexate content determination, take a sample of 10u1 and inject it into a liquid chromatograph, record the chromatogram; Take an appropriate amount of methotrexate reference substance, weigh it precisely, add the mobile phase to dissolve and quantitatively dilute it to about 0 per 1 ml. lmg solution, the same method of determination, according to the external standard method to calculate the peak area, that is.
Same as methotrexate.
2.5mg
light shielding, sealed storage.
This product is the sodium salt of methotrexate and sodium chloride appropriate sterile freeze-dried product. Based on the average loading, methotrexate (C20H22N805) should be 95.0% to 110.0% of the labeled amount.
This product is yellow or brown loose blocks or powder.
determination of content
take the contents under the item of difference in loading, mix well, weigh an appropriate amount (about 10mg equivalent to methotrexate) precisely, add mobile phase to dissolve and quantitatively dilute to about 0% methotrexate per 1 ml. The solution of 1 mg was obtained as a test solution by measurement according to the method under the item of methotrexate content measurement. (5mg specification based on mean content uniformity)
category
Same as methotrexate.
specification
(l ) 5mg (2 )0.lg ( 3 ) lg
storage
shade, close, and store in a cool place.