3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Names and Identifiers
Name | josamycin
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Synonyms | YL-704A3 Vilprafen Wilprafen josamycin Josamycin solution Josamycin Solution, 100ppm Josamycin for peak identification 3-Acetate 4B-(3-Methylbutanoate)leucoMycin V LeucoMycin V, 3-acetate4B-(3-Methylbutanoate) Leucomycin V 3-acetate 4''-(3-methylbutanoate) 6-{[6-{[(4R,5S,6S,7R,9R,10R,11E,13E,16R)-4-(acetyloxy)-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)oxacyclohexadeca-11,13-dien-6-yl]oxy}-4-(dimethylamino)-5-hydroxy-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate (non-preferred name) (2S,3R,4R,6S)-6-{[(2R,3S,4R,5R,6S)-6-{[(4R,6S,7R,9R,10R,11E,13E,16R)-4-(acetyloxy)-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)oxacyclohexadeca-11,13-dien-6-yl]oxy}-4-(dimethylamino)-5-hydroxy-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate (non-preferred name) (2S,3S,4R,6S)-6-{[(2R,3S,4R,5R,6S)-6-{[(4R,5S,6S,7R,9R,10R,11E,13E,16R)-4-(acetyloxy)-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)oxacyclohexadeca-11,13-dien-6-yl]oxy}-4-(dimethylamino)-5-hydroxy-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate (non-preferred name)
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CAS | 16846-24-5
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EINECS | 240-871-6 |
InChI | InChI=1/C42H69NO15/c1-23(2)19-32(47)56-40-27(6)53-34(22-42(40,8)50)57-37-26(5)54-41(36(49)35(37)43(9)10)58-38-29(17-18-44)20-24(3)30(46)16-14-12-13-15-25(4)52-33(48)21-31(39(38)51-11)55-28(7)45/h12-14,16,18,23-27,29-31,34-41,46,49-50H,15,17,19-22H2,1-11H3/b13-12+,16-14+/t24-,25-,26?,27?,29+,30+,31-,34?,35?,36?,37?,38+,39+,40?,41?,42?/m1/s1 |
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Physico-chemical Properties
Molecular Formula | C42H69NO15
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Molar Mass | 827.99 |
Density | 1.1547 (rough estimate) |
Melting Point | 131.5℃ |
Boling Point | 763.27°C (rough estimate) |
Specific Rotation(α) | D25 -70° (c = 1 in ethanol) |
Flash Point | 484.7°C |
Solubility | Soluble in ethanol |
Vapor Presure | 0mmHg at 25°C |
Appearance | powder |
Color | white to slightly yellow |
Merck | 13,5286 |
pKa | 7.1 (40% aq methanol) |
Storage Condition | Inert atmosphere,Store in freezer, under -20°C |
Refractive Index | 1.6220 (estimate) |
MDL | MFCD00211043 |
In vitro study | Studies show that the average lifetime on the ribosome is 3 h for Josamycin and that the dissociation constants for Josamycin binding to the ribosome is 5.5 nM. Josamycin slows down formation of the first peptide bond of a nascent peptide in an amino acid-dependent way and completely inhibits formation of the second or third peptide bond, depending on peptide sequence at a saturating drug concentration, synthesis of fulllength proteins is completely shut down by Josamycin. At a saturating drug concentration, synthesis of fulllength proteins is completely shut down by Josamycin. |
In vivo study | Blood and tissue levels of Josamycin after oral administration are 200 mg/kg to rabbits. Tissue levels are generally much higher than the blood levels, and 3 h after the administration, when the blood level is very low, the tissue levels are rather higher than those 1 h after the dose. One hour after the medication, the level in the lungs is the highest of all the tissue levels. |
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Risk and Safety
WGK Germany | 2 |
RTECS | OH4725810 |
FLUKA BRAND F CODES | 10 |
Toxicity | LD50 oral in rat: > 7gm/kg |
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Reference
Reference Show more | 1. Chen Shuxin, Wang Jing, He Shichong, Liu Zhengzheng, Feng Huajun, Mu Pengqian. Determination of 17 Antibiotics in Water by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry [J]. China Environmental Monitoring, 2020,36(06):119-126. |
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Standard
Authoritative Data Verified Data
This product is prepared with kitasamycin A3 [(4R,5S,6S,7R,9R,10R,llE ,13E,16R)-4-(Acetoxy)-6-[[3, 6-dideoxy-4-0-[2, 6-dideoxy-3-c-methyl-4-o-methylbutyrylpyran-hexosyl]-3-(dimethylamino)-B-D-glucopyranosyl] oxy]-10-hydroxy-5-methoxy-9, 16-dimethyl -7-(2-oxoethyl) oxadiane -11,13-diene -2-ketone]-based multi-component antibiotics. Based on the dry product, the titer of each lmg should not be less than 920 josamycin units.
Last Update:2024-01-02 23:10:35
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Trait
Authoritative Data Verified Data
- This product is white or off-white powder.
- This product is easily soluble in methanol, ethanol or ether, and slightly soluble in water.
specific rotation
take this product, precision weighing, plus absolute ethanol dissolution and quantitative dilution of the solution containing about 10 mg per 1 ml, according to the law (General 0621), the specific rotation is from one to 67 ° to one to 73 °.
Last Update:2022-01-01 11:54:02
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Differential diagnosis
Authoritative Data Verified Data
- Take 2mg of this product, add 5ml sulfuric acid, slowly shake, that is red-brown.
- take the standard sample of this product and josamycin, add methanol to dissolve and dilute to prepare a solution containing about 1 mg of josamycin per 1 ml, which is used as the test solution and the standard solution; according to the thin layer chromatography (General 0502) test, absorb 10 u1 of each of the above two solutions, respectively point on the same silica gel G thin layer plate, with n-hexane-acetone (8:7) as the developing solvent, after development, the mixture was dried, sprayed with a developer (phosphomolybdic acid in ethanol solution 1-10), and heated at 110 ° C. For 10 minutes. The position and color of the main spot displayed by the test solution should be the same as the position and color of the main spot of the standard solution.
- take the standard of this product and josamycin, add acetonitrile to dissolve and dilute to make it contain about 3 0 of kitasamycin per 1 ml. The retention time of the peak of the main component of the test solution should be consistent with the retention time of the kitasamycin A3 peak in the standard solution according to the chromatographic condition test under the item of the component of the lmg solution.
- take this product, add methanol to dissolve and dilute to make a solution containing about 20ug per lml, and measure by UV-Vis spectrophotometry (General 0401), there is an absorption maximum at a wavelength of 231mn.
- The infrared absorption spectrum of this product should be consistent with that of the control (Spectrum set 1135).
- two items (2) and (3) above can be selected as one item.
Last Update:2022-01-01 11:54:03
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Exam
Authoritative Data Verified Data
Related substances
take the right amount of this product, precision weighing, add acetonitrile to dissolve and quantitatively dilute to make a solution containing about 1 mg of kitasamycin A3 per 1 ml, as a test solution; in addition, the appropriate amount of josamycin standard was accurately weighed, dissolved with acetonitrile and quantitatively diluted to prepare a solution containing about 10ug of kitasamycin A3 per 1 ml, which was used as the standard solution; The appropriate amount of standard solution was accurately measured, A solution containing about 0.5ug of kitasamycin A3 per 1 μl was prepared as a sensitivity solution by quantitative dilution with acetonitrile. According to the chromatographic conditions under the item of tosamycin component, the sensitivity solution 20u1 is injected into the liquid chromatograph, and the signal-to-noise ratio of the peak height of kitasamycin A3 should be greater than 10. Accurately take 20 u1 of the test solution and the standard solution, respectively inject the human liquid chromatograph, record the chromatogram, if there are impurity peaks in the chromatogram of the test solution, according to the peak area of kitasamycin A3 calculated by external standard method, containing impurity B, impurity C, impurity D (relative retention time is about 0.90,0.78,0.98) are not more than 2.0%, impurity E (relative retention time is about 1.15) shall not exceed 5.0%, other individual impurities shall not exceed 2.0%, and the total amount of impurities shall not exceed 8.0%. The peaks in the chromatogram of the test solution which are smaller than the main peak area of the sensitivity solution are ignored.
residual solvent
take about lg of this product, weigh it accurately, put it in a 10ml measuring flask, add 0.12% ml of internal standard solution (1.0 ethylphenylacetone solution), dilute it with acetone to the scale, shake, as a test solution; Another precision weigh the appropriate amount of toluene, quantitative dilution with acetone to make a solution containing about 0.8mg per 1 ml. Take 1 ml, put it in a 10ml measuring flask, add 1.0ml of internal standard solution, dilute it to the scale with acetone, shake well, and use it as a reference solution. According to the residual solvent measurement method (General 0861 third method), the divinylbenzene-styrene type polymer porous beads were used as the stationary phase, and the column temperature was 190°C. 2 u1 of the test solution and the reference solution are respectively injected into the gas chromatograph, the chromatogram is recorded, and the peak area ratio is calculated according to the internal standard method. The residual amount of toluene shall be in accordance with the regulations.
loss on drying
take this product, with phosphorus pentoxide as desiccant, at 60°C under reduced pressure drying to constant weight, weight loss should not exceed 2.0% (General rule 0831).
ignition residue
take l.Og of this product and determine it according to law (General rule 0841). The remaining residue shall not exceed 0.2%.
Heavy metals
The residue left under the ignition residue item shall not contain more than 30 parts per million of heavy metal when examined by law (General rule 0821, Law II).
josamycin component
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded gel as filler (4.6mm X 250mm ,5um or equivalent column); with high gas acid solution (take 119g of sodium perchlorate monohydrate, add water to dissolve and dilute to 1000ml, adjust the pH value to 2.5 with 1 mol/ L hydrochloric acid solution)-acetonitrile-tetrahydrofuran (152:94:4) mobile phase 8, acetonitrile is mobile Phase B, linear gradient elution is carried out according to the following table, the detection wavelength is 231nm, and the column temperature is 25-30°C. Take an appropriate amount of josamycin standard, add acetonitrile to dissolve and dilute to make a solution containing 1 mg of kitasamycin A3 per 1 ml, and inject 20u1 into human liquid chromatograph, the chromatogram recorded should be consistent with the standard chromatogram of the josamycin standard (the retention time of the kitasamycin A3 peak is about 40 minutes. Dissolve 50ml of lmol/ L potassium dihydrogen phosphate solution (adjusted to pH 2.0 with phosphoric acid), heat it in a 40°C water bath for 3 hours, remove it, cool it, and use 2mol/ L sodium hydroxide
.
- adjust the pH value to 7.0±0.2, add 50ml of methanol, mix well to obtain a mixed solution of josamycin and impurity D (relative retention time is about 0.9), and inject 20M1 into human liquid chromatograph, record chromatogram, the degree of separation between kitasamycin A3 peak and impurity D peak should be not less than 1.0.
assay
take the right amount of this product, precision weighing, add acetonitrile to dissolve and quantitatively dilute to make a solution containing about 1 mg of kitasamycin A3 per 1 ml, as a test solution; in addition, an appropriate amount of josamycin standard was accurately weighed, dissolved with acetonitrile and quantitatively diluted to prepare a solution containing 1 mg of kitasamycin A3 per 1 ml, which was used as the standard solution. Accurately take 20 u1 of the test solution and the standard solution, respectively inject into the liquid chromatograph, record the chromatogram, calculate the peak area of kitasamycin A3 according to the external standard method, and calculate according to the dry product, kitasamycin A3 should not be less than 87.0%; Kitasamycin A1, A3, A4, A6, A7 and midecamycin eight, the sum of components (relative retention time is about 0.88,1.0,0.80,0.52,0.38,0.82) should not be less than 90.0%.
Last Update:2022-01-01 11:54:04
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Content determination
Authoritative Data Verified Data
take an appropriate amount of this product, precision weighing, add an appropriate amount of ethanol (3ml of ethanol per 10 mg) to dissolve, and then dilute quantitatively with sterile water to make a solution containing about 1000 units per 1 ml, according to the microbiological assay of antibiotics (General 1201). 1000 josamycin unit is equivalent to 1 mg josamycin.
Last Update:2022-01-01 11:54:05
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Category
Authoritative Data Verified Data
Last Update:2022-01-01 11:54:05
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Storage
Authoritative Data Verified Data
shading and preservation.
Last Update:2022-01-01 11:54:05
3-Acetate 4B-(3-Methylbutanoate)leucoMycin V - Josamycin tablets
Authoritative Data Verified Data
This product contains josamycin (C42H69NO15) should be labeled the amount of 90.0% ~ 110.0%.
trait
This product is a Tang-coated tablet or film-coated tablet, which shows white or off-white color after removing the coating.
identification
- take an appropriate amount of the fine powder of this product, add methanol to dissolve and dilute josamycin to make a solution containing about 1 mg of josamycin per 1 ml, filter, and take the continued filtrate as the test solution, according to the identification (2) test under the item of the item, the sample amount is 5 u1, and the same result should be shown.
- take an appropriate amount of fine powder of this product, add methanol to dissolve and make a solution containing about 20ug of josamycin per lml, filter, and take the filtrate as the identification (4) test under the item of josamycin, the same results should be shown.
examination
- weight loss on drying this product shall be dried under reduced pressure at 60°C for 3 hours with phosphorus pentoxide as desiccant, and the weight loss shall not exceed 5.0% (General rule 0831).
- dissolution: according to the dissolution and release determination method (General rule 0931, second method), dissolve 4.5g of potassium dihydrogen phosphate in phosphate buffer (pH 13.61), and add of water, adjust the pH value to 4.5 with sodium hydroxide solution, add water 1000ml)900ml as dissolution medium, rotate at 50 rpm, operate according to law, after 30 minutes, take appropriate amount of solution, filter, accurately take appropriate amount of continued filtrate, quantitatively dilute with dissolution medium to make a solution containing about 20ug of josamycin per lml, and perform UV-Vis spectrophotometry (General rule 0401),
at a wavelength of 231nm
- absorbance: Take 10 tablets of this product, grind them finely, weigh them accurately and take an appropriate amount (equivalent to the average tablet weight), dissolve and quantitatively dilute them according to the labeled amount and dissolution medium to make them contain about 0 per lml. 1 mg of the solution is filtered, and the filtrate is accurately taken and diluted quantitatively with the dissolution medium to prepare a solution containing about 20ug of josamycin per 1 ml. The dissolution amount of each tablet is calculated by the same method. The limit is 75% 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
Take 10 tablets of this product, precision weighing, fine grinding, precision weighing an appropriate amount (equivalent to 0.2g of josamycin), plus an appropriate amount of ethanol (3ml of ethanol per 10 mg) the josamycin was dissolved by ultrasound, and then quantitatively diluted with sterilized water to prepare a solution containing about 1000 units per 1 ml, which was determined according to the method under the item of josamycin. 1000 josamycin units are equivalent to lmg C42H69N015.
category
same josamycin.
specification
(l)50mg (50,000 units) (2)0.2g (200,000 units)
storage
sealed and stored in a dry place.
Last Update:2022-01-01 11:54:06