Arteannuinum - Names and Identifiers
Name | Artesunate
|
Synonyms | Artesunate ARTESUNATE ARTENSUNATE Arteannuinum Artesunic Acid ArtesunateC19H28O8 Arteannuinum succinate Artemisinin monosuccinate (3R,5aS,6R,8aS,9R,10S,12R,12aR)-Decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin-10-ol hydrogen succinate 4-oxo-4-{[(5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl]oxy}butanoic acid 4-oxo-4-{[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl]oxy}butanoic acid Butanedioic Acid Mono(3R,5aS,6R,8aS,9R,10R,12R,12aR)-decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin-10-yl] Ester Butanedioic acid, 1-[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin-10-yl] ester Artesunate (3R,5aS,6R,8aS,9R,10S,12R,12aR)-Decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin-10-ol hydrogen succinate
|
CAS | 88495-63-0
|
EINECS | 618-170-5 |
InChI | InChI=1/C19H28O8/c1-10-4-5-13-11(2)15(16(22)23-9-7-14(20)21)24-17-19(13)12(10)6-8-18(3,25-17)26-27-19/h10-13,15,17H,4-9H2,1-3H3,(H,20,21)/t10-,11-,12+,13+,15-,17-,18-,19?/m1/s1 |
Arteannuinum - Physico-chemical Properties
Molecular Formula | C19H28O8
|
Molar Mass | 384.42 |
Density | 1.2076 (rough estimate) |
Melting Point | 132-1350C |
Boling Point | 431.1°C (rough estimate) |
Solubility | DMSO : 83.33 mg/mL (216.77 mM; Need ultrasonic);H2O : < 0.1 mg/mL (insoluble) |
Appearance | Powder |
Color | white to off-white |
Merck | 14,818 |
pKa | 4.28±0.17(Predicted) |
Storage Condition | 2-8°C |
Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month. |
Sensitive | Sensitive to heat |
Refractive Index | 1.4430 (estimate) |
MDL | MFCD00866204 |
Arteannuinum - Risk and Safety
Hazard Symbols | Xn - Harmful
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Risk Codes | 20/21/22 - Harmful by inhalation, in contact with skin and if swallowed.
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Safety Description | 24/25 - Avoid contact with skin and eyes.
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WGK Germany | 3 |
HS Code | 29419090 |
Arteannuinum - Reference
Reference Show more | 1. Li Yafen, Zhao Jun, LV Guodong, et al. Study on the anti-Echinococcus granulosus mechanism of Veliparib combined with artesunate in vitro [J]. Chinese Journal of pathogenic biology, 2018v.13;No.139(07):59-65. 2. Zheng Haiya, Wen Limei, Lu Guodong, etc. Study on the effect of artesunate against Echinococcus granulosus active oxygen on DNA mechanism in vitro [J]. Chinese Journal of pathogenic biology, 2017, 29 (08):751-756. 3. Zhu Chunyan, Xu Qiong, Mao Zhiyun, etc. Comparison of effects of three artemisinin derivatives on pain co-emotion disorder in mice with neuropathic pain [J]. Chinese Journal of Traditional Chinese Medicine 2018(15). 4. Wu Xuan, Su Xiaohui, Meng Xianghe, Wang Xin, Kong Xiangying, Lin Na. Comparative analysis of artemisinin and its derivatives on osteoclast differentiation [J]. Chinese Journal of Experimental prescriptions, 2018,24(04):84-89. 5. Zheng, Chuanrui, et al. "Cardiotoxicity and cardioprotection by artesumate in larval zebra fish." Dose-Response 18.1 (2020): 1559325819897180.https://doi.org/10.1177/1559325819897180 6. [IF = 6.529] Xiaohui Su et al."Artesunate attenuates bone erosion in rheumatoid arthritis by suppressing reactive oxygen species via activating p62/Nrf2 signaling."Biomed Pharmacother. 2021 May;137:111382 7. [IF=2.738] Li Y. F. et al."In Vitro and In Vivo Efficacy of DNA Damage Repair Inhibitor Veliparib in Combination with Artesunate against Echinococcus granulosus."Dis Markers. 2020;2020:8259820 8. [IF=2.658] Chuanrui Zheng et al."Cardiotoxicity and Cardioprotection by Artesunate in Larval Zebrafish:."Dose-Response. 2020;18(1): |
Arteannuinum - Standard
Authoritative Data Verified Data
This product is dihydroartemisinin-10a-succinate monoester. The content of C19H2808 shall be between 98.0% and 102.0% calculated as anhydrous.
Last Update:2024-01-02 23:10:35
Arteannuinum - Trait
Authoritative Data Verified Data
- This product is white crystalline powder; Odorless.
- This product is soluble in ethanol, acetone or methylene chloride, and is very slightly soluble in water.
specific rotation
take this product, precision weighing, add methylene chloride to dissolve and quantitatively dilute the solution containing 25mg per lml, and determine according to law (General 0621), the specific rotation was 4.5 ° to 6.5 °.
Last Update:2022-01-01 13:32:46
Arteannuinum - Introduction
Artesunate is a semi-synthetic artemisinin derivative, which has been proven to be effective against parasites, such as liver flukes, and is an antimalarial drug. It also shows cytotoxic effects on different types of tumor cell lines and is an inhibitor of STAT-3 and export protein 1 (EXP1). This product can be used for scientific research experiments in related fields. Artemisia annua ester Artesunate is an inhibitor of STAT-3 and export protein 1 (EXP1).
Last Update:2022-10-16 17:29:35
Arteannuinum - Differential diagnosis
Authoritative Data Verified Data
- This product was dissolved and diluted with methanol to prepare a solution containing 1mg in μl ml as a test solution; Another 10 mg of artesunate reference product was dissolved with 10ml of methanol as a reference solution. According to the thin layer chromatography (General 0502) test, Draw 5 u1 of each of the above two solutions, respectively point on the same silica gel G thin layer plate, with ethanol-toluene-concentrated ammonia test solution (70:30:1.5) as the developing solvent, it is spread out, taken out to dry, sprayed with sulfuric acid ethanol solution containing 2% vanillin (20-100), heated at 120°C for 5 minutes, and examined in sunlight, the position and color of the main spot displayed by the test solution should be consistent with the main spot of the artesunate control solution.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
- The infrared absorption spectrum of this product should be consistent with that of the control (Spectrum set 221).
- two items (1) and (2) above can be selected as one item.
Last Update:2022-01-01 13:32:47
Arteannuinum - Exam
Authoritative Data Verified Data
acidity
take 0.20g of this product, add 20ml of water, shake, and determine according to law (General 0631), the pH value should be 3.5~4.5.
clarity and color of solution
take 0.60g of this product and add 6mL of 5% sodium bicarbonate solution to dissolve the solution. The solution should be clear and colorless; If it is turbid, compare it with No. 1 turbidity standard solution (General rule 0902 first method), not more concentrated. (For injection)
chloride
take 0.25g of this product, add 25ml of water, shake, filter, take and continue the filtrate to check according to law (General rule 0801), in case of turbidity, with standard sodium chloride solution 5.0 ml of the control solution should not be more concentrated (0.02%).
Related substances
take the test solution under the content determination item as the test solution; Take 1ml with precision, put it in a 100ml measuring flask, dilute it with acetonitrile to the scale, and shake it well, as a control solution. According to the chromatographic conditions under the content determination item, 20ul of each of the control solution and the test 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 is a chromatographic peak in the chromatogram of the test solution that is consistent with the retention time of the peak of dihydroartemisinin (two chromatographic peaks), the sum of the two peak areas shall not be greater than the main peak area of the control solution (1.0% ) , if there is a chromatographic peak with the same retention time as artemisinin, the peak area shall not be greater than 0.5 times (0.5%) of the main peak area of the control solution. (Relative retention time is about 2.7) for chromatographic peaks with the same retention time, the peak area shall not be greater than 0.07 times (0.2) of the main peak area of the control solution after multiplying the correction factor by 0.2%, other single impurity peak area shall not be greater than 0.2 times (0.2%) of the main peak area of the control solution, the sum of each impurity peak area (impurity I Peak area multiplied by the correction factor of 0.07) not more than 2 times (2.0%) the area of the main peak of the control solution. The chromatogram of the test solution is 0.05 times (0.05%) smaller than the main peak area of the control solution.
moisture
take 0.5g of this product, according to the determination of moisture (General 0832 first method 1), the water content shall not exceed 0.5%.
ignition residue
take l.Og of this product and check it according to law (General rule 0841). The residue left shall not exceed 0.1%.
Heavy metals
The residue left under the item of ignition residue shall be taken and inspected according to law (General Principles 0821, Law II) to contain no more than 20 parts per million of heavy metals.
bacterial endotoxin
take this product, check according to law (General 1143), the amount of endotoxin per 1 mg artesunate should be less than 1.25EU. (For injection)
sterile
take this product, add appropriate solvent to dissolve and dilute, after the membrane filtration method, according to the law inspection (General 1101), should comply with the provisions. (For aseptic dispensing)
Last Update:2022-01-01 13:32:48
Arteannuinum - Content determination
Authoritative Data Verified Data
measured by high performance liquid chromatography (General 0512).
chromatographic conditions and system suitability test
silica gel bonded with octa-alkyl silane as filler [phenmenex Luna C18(2) , 4.6mm X 100mm,3um or equivalent column]; Acetonitrile-phosphate buffer (take potassium dihydrogen phosphate 1.36g, add water 900ml to dissolve, adjust pH to 3.0 with phosphoric acid, add water to 1000ml) (44:56) as mobile phase, flow rate is 1.0ml per minute; Column temperature is 30°C; the detection wavelength was 216nm. Take 10mg of dihydroartemisinin control sample and 10mg of artemisinin control sample, put them in 10ml measuring flask, dissolve them with acetonitrile and dilute them to the standard, and use them as mixed impurity control solution; Take 10mg of artesunate control sample, put them in 10ml measuring flask, add 1ml mixed impurity reference solution, add appropriate amount of acetonitrile to dissolve and dilute to the scale, as the system applicable solution, take 20u1 injection liquid chromatography, record chromatogram. The relative retention times of the artesunate peak (retention time of about 9 minutes), two dihydroartemisinin peaks and artemisinin peaks were about 1.0, 0.58, 0.91 and 1.30, respectively. The ratio of the peak height of the second chromatographic peak of dihydroartemisinin to the valley height between the second chromatographic peak of dihydroartemisinin and the peak of artesunate should be greater than 5.0.
assay
take about 40mg of this product, accurately weigh, put it in a 10ml measuring flask, add acetonitrile to dissolve and dilute to the scale, shake well, as a test solution, the chromatogram was recorded by injection of 20u1 into human liquid chromatograph, and artesunate reference substance was taken for determination by the same method. According to the external standard method to calculate the peak area, that is.
Last Update:2022-01-01 13:32:48
Arteannuinum - Category
Authoritative Data Verified Data
Last Update:2022-01-01 13:32:49
Arteannuinum - Storage
Authoritative Data Verified Data
shade, seal, and store in a cool place.
Last Update:2022-01-01 13:32:49
Arteannuinum - Artesunate tablets
Authoritative Data Verified Data
This product contains artesunate (C19H2808) should be 90.0% to 110.0% of the label amount.
trait
This product is a white tablet or film-coated tablet, White after removal of the coating.
identification
- take an appropriate amount of the fine powder of this product (about 10mg of artesunate), add 10ml of methanol to dissolve, filter, take the filtrate as the test solution; Take the artesunate reference material lOmg, add 10ml of methanol to dissolve, as a control solution. According to the thin layer chromatography (General 0502) test, Draw 5 u1 of each of the above two solutions, respectively point on the same silica gel G thin layer plate, with ethanol-toluene-concentrated ammonia test solution (70:30:1.5) as the developing solvent, it is spread out, taken out to dry, sprayed with 2% vanillin in sulfuric acid ethanol solution (20- 100), heated at 120°C for 5 minutes, and examined in sunlight, the position and color of the main spot displayed by the test solution should be consistent with the main spot of the artesunate control solution.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
- take an appropriate amount of fine powder of this product (about 0.1g of artesunate), add 15ml of acetone to shake to dissolve, filter, evaporate the filtrate to dryness, and dry the residue under reduced pressure with silica gel as desiccant. According to infrared spectrophotometry (General 0402), the infrared absorption spectrum of this product should be consistent with the control spectrum (Spectrum set 221).
- two items (1) and (2) above can be selected as one item.
examination
- for related substances, take the test solution under the content determination item as the test solution; Take 1ml of precision measurement, put it in a 100ml measuring flask, dilute it to the scale with acetonitrile, and shake it well, as a control solution. According to the method of artesunate related substances. In the chromatogram of the test solution, if there is a chromatographic peak with the same retention time as the peak of dihydroartemisinin (two chromatographic peaks), the sum of the two peak areas shall not be greater than 2.5 times (2.5%) of the main peak area of the control solution. If there are chromatographic peaks with the same retention time as artemisinin, the peak area shall not be greater than 0.5 times (0.5%) of the main peak area of the control solution. If there are chromatographic peaks with retention time consistent with impurity I (relative retention time is about 2.7), the peak area multiplied by the correction factor of 0.07 shall not be greater than 0.3 times (0.3%) of the main peak area of the control solution, and the peak area of other individual impurities shall not be greater than 0.3 times (0.3%) of the main peak area of the control solution, the sum of the peak areas of each impurity (calculated by multiplying the peak area of impurity I by the correction factor of 0.07) shall not be greater than 3.5 times (3.5%) the area of the main peak of the control solution. The chromatogram of the test solution is 0.1 times (0.1%) smaller than the main peak area of the control solution.
- dissolution dissolution of this product, according to the dissolution and release determination method (General rule 0931 second method), with phosphate buffer solution (sodium dihydrogen phosphate 6.9g, sodium hydroxide 0.9g, add water 800ml to dissolve, adjust pH to 6.8 with 2mol/L sodium hydroxide solution, dilute with water to 1000ml)900ml as dissolution medium, speed is 75 rpm, operate according to law, after 45 minutes, filter, take filtrate, as a test solution (immediate determination); Take artesunate reference about 12.5mg, precision weighing, put in 25ml measuring flask, add appropriate amount of acetonitrile dissolved and diluted to the scale, shake, take an appropriate amount of precision, and dilute quantitatively by adding dissolution medium to prepare a solution containing about 0.05mg(50mg specification) or 0.lmg(lOOmg specification) per 1 ml, which is used as a reference solution (ready to use new system). With eighteen alkyl silane bonded silica gel as filler (4.6mm x 250mm,5um or performance equivalent column), with acetonitrile-phosphate buffer (take potassium dihydrogen phosphate 1.36g, add water 900ml to dissolve, the pH value was adjusted to 3.0 with phosphoric acid, and water was added to 1.5ml) (50:50) as mobile phase; The flow rate was ml per minute; The column temperature was 30 ° C.; The detection wavelength was 210nm. 100ul of the test solution and the reference solution were respectively injected into the human liquid chromatograph, and the chromatograms were recorded. The dissolution amount of each tablet was calculated by the peak area according to the external standard method. The limit is 80% of the labeled amount and shall be in accordance with the provisions.
- others shall be in accordance with the relevant provisions under the item of tablets (General rule 0101).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica gel as filler [phenmenex Luna C18(2) ,4.6mm x 100mm,3um or performance equivalent column]; the mobile phase is acetonitrile-phosphate buffer (1.36g of dihydrogen phosphate, of water is added to dissolve the solution, pH is adjusted to 3.0 with phosphoric acid, and of water is added)(44:56), the flow rate was 1.0ml per minute; The column temperature was 30°C; The detection wavelength was 216mn. Take 10mg of dihydroartemisinin control sample and 10mg of artemisinin control sample, put them in 10ml measuring flask, dissolve them with acetonitrile and dilute them to the standard, and use them as mixed impurity control solution. Take 10mg of artesunate control sample, put them in 10ml measuring flask, add 1ml of mixed impurity reference solution, add appropriate amount of acetonitrile to dissolve artesunate and dilute to the scale, as the system applicable solution, take 20u1 injection human liquid chromatograph, record chromatogram. The relative retention times of the peak of artesunate (the retention time was about 9 minutes) and the two dihydroartemisinin peaks were about 1.0,0.58,0.91 and 1.30, respectively. The ratio of the peak height of the second chromatographic peak of dihydroartemisinin to the valley height between the second chromatographic peak of dihydroartemisinin and the peak of artesunate should be greater than 5.0.
- determination of 10 tablets of this product, precision weighing, fine grinding, precision weighing an appropriate amount (about 40mg equivalent to artesunate), put in a 10ml measuring flask, add an appropriate amount of acetonitrile, ultrasonic dissolution, cool, dilute to the scale with acetonitrile, shake, filter, as a test solution, take 20ul injection of human liquid chromatograph, record the chromatogram; Take an appropriate amount of artesunate reference, precision weighing, plus acetonitrile dissolved and quantitative dilution of each 1 ml containing about 4mg of the solution, the same method. According to the external standard method to calculate the peak area, that is.
category
with artesunate.
specification
(l)50mg (2)100mg
storage
light shielding, sealed storage.
Last Update:2022-01-01 13:32:50
Arteannuinum - Artesunate for Injection
Authoritative Data Verified Data
This product is sterile powder of artesunate. The artesunate (C19H2808) content shall be 98.0% to 102.0% based on the water content and the cyanhydrin ester (C19H2808) content shall be 93.0% to 110.0% of the labeled amount based on the average loading.
trait
This product is a white crystalline powder.
identification
- This product was dissolved in methanol and diluted to prepare a solution containing 1 mg per 1 ml as a test solution. In addition, 10 mg of artesunate reference product was dissolved in 10ml of methanol as a reference solution. According to the thin layer chromatography (General 0502) test, absorb 5ul of each of the above two solutions, respectively point on the same silica gel G thin layer plate, with ethanol-toluene-concentrated ammonia test solution (70:30:1.5) as the developing solvent, spread out, take it out and dry it, spray it with a sulfuric acid ethanol solution containing 2% vanillin (20-100), heated at 120°C for 5 minutes, and examine it in sunlight, the position and color of the main spot displayed by the test solution should be consistent with the main spot of the artesunate control solution.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
- The infrared absorption spectrum of this product should be consistent with that of the control (Spectrum set 221).
- two items (1) and (2) above can be selected as one item.
examination
- acidity: take 0.20g of this product, add 20ml of water, shake, and measure according to law (General rule 0631). The pH value should be 3.5~4.5.
- the clarity and color of the solution take 0.60g of this product, add Artesunate for Injection special solvent 6ml to dissolve, the solution should be clear and colorless; If it is turbid, compared with No. 1 turbidity standard solution (General Principles 0902 first method), should not be more concentrated.
- chloride take 0801g of this product, add water, shake, filter, take the filtrate and continue to check according to law (general rule), in case of turbidity, it should not be more concentrated (0.02%) than the control solution made up of the standard gasification sodium solution.
- for related substances, take the test solution under the content determination item as the test solution; Take 1 ml for precise measurement, put it in a 100ml measuring flask, dilute it to the scale with acetonitrile, and shake it well, as a control solution. According to the method of artesunate related substances. If there is a chromatographic peak in the chromatogram of the test solution that is consistent with the retention time of the peak of dihydroartemisinin (two chromatographic peaks), the sum of the two peak areas shall not be greater than the main peak area of the control solution (1.0% ), if there are chromatographic peaks with the same retention time of artemisinin, the peak area shall not be greater than 0.5 times (0.5%) of the main peak area of the control solution, if there is impurity 1 (relative retention time is about 2.7) for chromatographic peaks with the same retention time, the peak area shall not be greater than 0.07 times (0.2) of the main peak area of the control solution after the peak area is multiplied by the correction factor of 0.2%, other single impurity peak area shall not be greater than 0.2 times (0.2%) of the main peak area of the control solution, and the sum of each impurity peak area (calculated by multiplying the peak area of impurity I by the correction factor of 0.07) not more than 2 times (2.0%) the area of the main peak of the control solution. The chromatogram of the test solution is 0.05 times (0.05%) smaller than the main peak area of the control solution.
- water content: take 0832g of this product and determine the content of water according to the method for determination of water content (General rule 0.5%, first method 1).
- bacterial endotoxin this product is dissolved in Artesunate for Injection special solvent and checked according to law (General rule 1143). The endotoxin in artesunate should be less than 1.25EU per 1 mg.
- others should comply with the relevant provisions under injection (General 0102).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica gel as filler [phenmenex Luna C18 (2 ),4.6mm x 100mm,3um or performance equivalent column]; using acetonitrile-phosphate buffer (take potassium dihydrogen phosphate 1.36g, add water 900ml to dissolve, adjust pH to 3.0 with phosphoric acid, add water to 1000ml)(44:56) as mobile phase, the flow rate was 1.0ml per minute; The column temperature was 30°C; The detection wavelength was 216mn. Take 10 mg of dihydroartemisinin control and 10ml of artemisinin control, add acetonitrile to dissolve and dilute to the scale, as a mixed impurity control solution; Take 10 mg of artesunate control and put it in 10ml measuring flask, add 1ml of mixed impurity reference solution, add appropriate amount of acetonitrile to dissolve artesunate and dilute to the scale, as the system applicable solution, take 20u1 injection human liquid chromatograph, record chromatogram. The relative retention times of artesunate peak (retention time about 9 minutes), two dihydroartemisinin peaks and artemisinin peak were about 1.0, 0.58 ,0.91 and 1.30, respectively. The ratio of the peak height of the second chromatographic peak of dihydroartemisinin to the valley height between the second chromatographic peak of dihydroartemisinin and the peak of artesunate should be greater than 5.0.
- determine the content under the item of loading amount difference, mix evenly, weigh about 40mg accurately, put it in a 10ml measuring flask, add acetonitrile to dissolve and dilute to the scale, shake well, as a sample solution, 20ul injection liquid chromatograph was used for precision measurement, and the chromatogram was recorded. Artesunate reference substance was also used for determination by the same method. According to the external standard method to calculate the peak area, that is.
category
with artesunate.
specification
60mg
storage
shade, close, and store in a cool place.
Last Update:2022-01-01 13:32:51
Arteannuinum - Biological activity
Artesunate is an antimalarial drug that acts on small cell lung cancer cell line H69 with an IC50 of <5 μm. It is a potential STAT3 inhibitor with a selective cytotoxic effect on cancer cells in vitro; It is a potent inhibitor of exp1. In vitro study of ART can change the biomechanical properties of glioma cells, inhibit cell proliferation, migration and invasion. ART can significantly inhibit SKM-1 cell proliferation, induce apoptosis, and promote cell cycle arrest in G0/G1 phase. The mechanism of ART against MDS is related to the increase of intracellular calcium concentration and ROS level. In addition, the pro-apoptotic activity of ART may be related to the regulation of BCL-2/BAX ratio and the expression of P-bad and survivin. ART treatment demethylates CDH1, thereby restoring E-cadherin activation in SKM-1 of cells.
Last Update:2023-08-16 21:32:38