Miconazole Nitrate Add Methanol to Make Exactly 20 Ml, and Use This Solution As the Standard Solution

JP XV O‹cial Monographs / Micronomicin Sulfate 893

sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 20 mL, pipet 1 mL of this solution, Miconazole Nitrate add methanol to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions ミコナゾール硝酸塩 as directed under Thin-layer Chromatography <2.03>. Spot 50 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of n-hexane, chloroform, methanol and ammonia solution (28) (60:30:10:1) to a distance of about 12 cm, and air-dry the plate. Allow the plate in iodine vapor for 20 minutes: the spots other than the principal spot from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, in vacuum, C18H14Cl4N2O.HNO3: 479.14 silica gel, 609C, 3 hours). 1-[(2RS)-2-(2,4-Dichlorobenzyloxy)-2-(2,4- Residue on ignition <2.44> Not more than 0.1z (1 g). dichlorophenyl)ethyl]-1H-imidazole mononitrate [22832-87-7 ] Assay Weigh accurately about 0.35 g of Miconazole Ni- trate, previously dried, dissolve in 50 mL of acetic acid (100) Miconazole Nitrate, when dried, contains not less by warming, cool, and titrate <2.50> with 0.1 molWL perchlor- than 98.5z of C18H14Cl4N2O.HNO3. ic acid VS (potentiometric titration). Perform a blank determination, and make any necessary correction. Description Miconazole Nitrate occurs as a white crystalline powder. Each mL of 0.1 molWL perchloric acid VS

It is freely soluble in N,N-dimethylformamide, sparingly ＝ 47.91 mg of C18H14Cl4N2O.HNO3 soluble in methanol, slightly soluble in ethanol (95), in ace- Containers and storage Containers—Tight containers. tone and in acetic acid (100), and very slightly soluble in Storage—Light-resistant. water and in diethyl ether. Melting point: about 1809C (with decomposition). Identiˆcation (1) To 2 mL of a solution of Miconazole Micronomicin Sulfate Nitrate in methanol (1 in 100) add 2 mL of Reinecke salt TS: a light red precipitate is formed. ミクロノマイシン硫酸塩 (2) Determine the absorption spectrum of a solution of Miconazole Nitrate in methanol (1 in 2500) as directed under Ultraviolet-visible Spectrophotometry <2.24>,andcompare the spectrum with the Reference Spectrum: both spectra ex- hibit similar intensities of absorption at the same wavelengths. (3) Perform the test with a solution of Miconazole Ni- trate in methanol (1 in 100) as directed under Flame Colora- tion Test <1.04> (2): a green color appears. (4) A solution of Miconazole Nitrate in methanol (1 in 100) responds to the Qualitative Tests <1.09> for nitrate. Purity (1) Clarity and color of solution—Dissolve 1.0 g of Miconazole Nitrate in 100 mL of methanol: the solution is 1 clear and colorless. C20H41N5O7.2 /2H2SO4:708.77 (2) Chloride <1.03>—Dissolve 0.10 g of Miconazole Ni- 2-Amino-2,3,4,6-tetradeoxy-6-methylamino-a-D- trate in 6 mL of dilute nitric acid and N,N-dimethylfor- erythro-hexopyranosyl-(1ª4)-[3-deoxy-4-C-methyl- mamide to make 50 mL. Perform the test using this solution 3-methylamino-b-L-arabinopyranosyl-(1ª6)]-2-deoxy-D- as the test solution. Prepare the control solution as follows: streptamine hemipentasulfate to 0.25 mL of 0.01 molWL hydrochloric acid VS add 6 mL of [52093-21-7, Micronomicin] dilute nitric acid and N,N-dimethylformamide to make 50 mL (not more than 0.09z). Micronomicin Sulfate is the sulfate of an (3) Heavy metals <1.07>—Proceed with 1.0 g of Micona- aminoglycoside substance having antibacterial activity zole Nitrate according to Method 2, and perform the test. produced by the growth of Micromonospora Prepare the control solution with 1.0 mL of Standard Lead sagamiensis. Solution (not more than 10 ppm). It contains not less than 590 mg (potency) and not (4) Arsenic <1.11>—Prepare the test solution with 1.0 g more than 660 mg (potency) per mg, calculated on the of Miconazole Nitrate according to Method 3, and perform anhydrous basis. The potency of Micronomicin Sulfate the test (not more than 2 ppm). is expressed as mass (potency) of micronomicin (5) Related substances—Dissolve 0.10 g of Miconazole (C20H41N5O7:463.57). Nitrate in 10 mL of methanol, and use this solution as the Description Micronomicin Sulfate occurs as a white to light 894 Midecamycin / O‹cial Monographs JP XV yellowish white powder. er. It is very soluble in water, sparingly soluble in ethylene (iii) Standard solutions—Weigh accurately an amount of glycol, and practically insoluble in methanol and in ethanol Micronomicin Sulfate Reference Standard, equivalent to (99.5). about 20 mg (potency), dissolve in 0.1 mol/L phosphate It is hygroscopic. buŠer solution for antibiotics, pH 8.0 to make exactly 20 mL, and use this solution as the standard stock solution. Identiˆcation (1) Dissolve 50 mg each of Micronomicin Keep the standard stock solution at 5 – 159C, and use within Sulfate and Micronomicin Sulfate Reference Standard in 10 30 days. Take exactly a suitable amount of the standard stock mL of water, and use these solutions as the sample solution solution before use, add 0.1 mol/L phosphate buŠer solution and the standard solution. Perform the test with these solu- for antibiotics, pH 8.0 to make solutions so that each mL tions as directed under Thin-layer Chromatography <2.03>. contains 2 mg (potency) and 0.5 mg (potency), and use these Spot 5 mL of the sample solution and standard solution on a solutions as the high concentration standard solution and low plate of silica gel for thin-layer chromatography. Develop the concentration standard solution, respectively. plate with a mixture of ethanol (99.5), 1-buthanol and ammo- (iv) Sample solutions—Weigh accurately an amount of nia solution (28) (10:8:7) to a distance of about 10 cm, and Micronomicin Sulfate, equivalent to about 20 mg (potency), air-dry the plate. Spray evenly a solution of ninhydrin in a and dissolve in 0.1 mol/L phosphate buŠer solution for an- mixture of acetone and pyridine (25:1) (1 in 500), and heat at tibiotics, pH 8.0 to make exactly 20 mL. Take exactly a suita- 1009C for 10 minutes: the spots obtained from the sample so- ble amount of this solution, add 0.1 mol/L phosphate buŠer lution and the standard solution are red-purple to red-brown solution for antibiotics, pH 8.0 to make solutions so that and their Rfvaluesarethesame. each mL contains 2 mg (potency) and 0.5 mg (potency), and (2) To 5 mL of a solution of Micronomicin Sulfate (1 in use these solutions as the high concentration sample solution 100) add 1 mL of barium chloride TS: a white precipitate is and low concentration sample solution, respectively. formed, and it does not dissolve by addition of dilute nitric acid. Containers and storage Containers—Tight containers.

20 Optical rotation <2.49> [a]D : ＋110 – ＋1309(0.25 g calculated on the anhydrous basis, water, 25 mL, 100 mm). Midecamycin pH <2.54> The pH of a solution obtained by dissolving 1.0 g of Micronomicin Sulfate in 10 mL of water is between 3.5 ミデカマイシン and 5.5. Purity (1) Clarity and color of solution—Dissolve 1.5 g of Micronomicin Sulfate in 10 mL of water: the solution is clear and colorless to pale yellow. (2) Heavy metals <1.07>—Proceed with 1.0 g of Micronomicin Sulfate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stan- dard Lead Solution (not more than 20 ppm). (3) Related substances—Dissolve 0.40 g of Micronomicin Sulfate in 10 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>.Spot5mLofthe C H NO :813.97 samplesolutionandstandardsolutiononaplateofsilicagel 41 67 15 (3 ,4 ,5 ,6 ,8 ,9 ,10 ,12 ,15 )- for thin-layer chromatography. Develop the plate with a mix- R R S R R R E E R 5-[2,6-Dideoxy-3-C-methyl-4-O-propanoyl-a-L-ribo- ture of ethanol (99.5), 1-buthanol and ammonia solution (28) hexopyranosyl-(1 4)-3,6-dideoxy-3-dimethylamino- -D- (10:8:7) to a distance of about 10 cm, and air-dry the plate. ª b glucopyranosyloxy]-6-formylmethyl-9-hydroxy-4-methoxy- Spray evenly a solution of ninhydrin in a mixture of acetone 8-methyl-3-propanoyloxyhexadeca-10,12-dien-15-olide and pyridine (25:1) (1 in 500), and heat at 1009Cfor10 [ ] minutes: the spot other than the principal spot obtained from 35457-80-8 the sample solution is not more intense than the spot from the standard solution. Midecamycin is a macrolide substance having antibacterial activity produced by the growth of Strep- Water <2.48> Not more than 10.0z (0.2 g, volumetric titra- tomyces mycarofaciens. tion, back titration). Use a mixture of methanol for water de- It contains not less than 950 mg (potency) and not termination and ethylene glycol for water determination (1:1) more than 1020 mg (potency) per mg, calculated on the instead of methanol for water determination. dried basis. The potency of Midecamycin is expressed Assay Perform the test according to the Cylinder-plate as mass (potency) of midecamycin (C41H67NO15). method as directed under Microbial Assay for Antibiotics Description Midecamycin occurs as a white crystalline pow- <4.02> according to the following conditions. der. (i) Test organism—Bacillus subtilis ATCC 6633 It is very soluble in methanol, freely soluble in ethanol (ii) Culture medium—Use the medium i in 1) Medium for (95), and very slightly soluble in water. test organism [5] under (1) Agar media for seed and base lay- Identiˆcation (1) Determine the absorption spectrum of a