{"id":13150,"date":"2025-10-13T10:16:20","date_gmt":"2025-10-13T03:16:20","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=13150"},"modified":"2025-11-15T15:38:23","modified_gmt":"2025-11-15T08:38:23","slug":"flucloxacillin-magnesium-octahydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/flucloxacillin-magnesium-octahydrate\/","title":{"rendered":"Flucloxacillin Magnesium Octahydrate"},"content":{"rendered":"

Flucloxacillin Magnesium<\/p>\n

(Ph. Eur. monograph 2346)<\/p>\n

C38<\/sub>H32<\/sub>Cl2<\/sub>F2<\/sub>MgN6<\/sub>O10<\/sub>S2<\/sub>,8H2<\/sub>O\u00a0 \u00a0 \u00a0 \u00a01074\u00a0 \u00a0 \u00a0 58486-36-5<\/p>\n

Action and use<\/strong><\/p>\n

Penicillin antibacterial.<\/p>\n

Preparations<\/strong><\/p>\n

Flucloxacillin Oral Suspension<\/p>\n

Co-fluampicil Oral Suspension<\/p>\n

DEFINITION<\/h2>\n

Magnesium bis[(2S,5R,6R)-6-[[[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate] octahydrate.<\/p>\n

Semi-synthetic product derived from a fermentation product.<\/p>\n

Content<\/h3>\n

95.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

White or almost white, crystalline powder.<\/p>\n

Solubility<\/h3>\n

Slightly soluble in water, freely soluble in methanol.<\/p>\n

IDENTIFICATION<\/h2>\n

First identification: A, C.<\/p>\n

Second identification: B, C.<\/p>\n

A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n

Comparison: flucloxacillin magnesium octahydrate CRS.<\/p>\n

B. Thin-layer chromatography (2.2.27).<\/p>\n

Test solution: Dissolve 25 mg of the substance to be examined in 5 mL of water R.<\/p>\n

Reference solution (a): Dissolve 25 mg of flucloxacillin sodium CRS in 5 mL of water R.<\/p>\n

Reference solution (b): Dissolve 25 mg of cloxacillin sodium CRS, 25 mg of dicloxacillin sodium CRS and 25 mg of flucloxacillin sodium CRS in 5 mL of water R.<\/p>\n

Plate: TLC silanised silica gel plate R.<\/p>\n

Mobile phase: Mix 30 volumes of acetone R and 70 volumes of a 154 g\/L solution of ammonium acetate R previously adjusted to pH 5.0 with glacial acetic acid R.<\/p>\n

Application: 1 \u03bcL.<\/p>\n

Development: Over 2\/3 of the plate.<\/p>\n

Drying: In air.<\/p>\n

Detection: Expose the plate to iodine vapour until the spots appear.<\/p>\n

System suitability: Reference solution (b):<\/p>\n

\u2014 the chromatogram shows 3 clearly separated spots.<\/p>\n

Results: The principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with reference solution (a).<\/p>\n

C. It gives the reaction of magnesium (2.3.1).<\/p>\n

TESTS<\/h2>\n

pH (2.2.3)<\/h3>\n

4.5 to 6.5.<\/p>\n

Dissolve 0.25 g in carbon dioxide-free water R and dilute to 50 mL with the same solvent.<\/p>\n

Specific optical rotation (2.2.7)<\/h3>\n

+ 163 to + 175 (anhydrous substance).<\/p>\n

Dissolve 0.250 g in water R and dilute to 50.0 mL with the same solvent.<\/p>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n

Test solution (a): Dissolve 50.0 mg of the substance to be examined in the mobile phase and dilute to 50.0 mL with the mobile phase.<\/p>\n

Test solution (b): Dilute 5.0 mL of test solution (a) to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (a): Dissolve 50.0 mg of flucloxacillin sodium CRS in the mobile phase and dilute to 50.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (b): Dilute 5.0 mL of test solution (b) to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (c): In order to prepare impurity A in situ, add 1 mL of sodium carbonate solution R to 10 mg of the substance to be examined, dilute to 25 mL with water R and place in an oven at 70 \u00b0C for 20 min.<\/p>\n

Reference solution (d): Dilute 1 mL of reference solution (c) to 10 mL with a 27 g\/L solution of dipotassium hydrogen phosphate R previously adjusted to pH 3.5 with dilute phosphoric acid R.<\/p>\n

Reference solution (e): In order to prepare impurity B in situ, add 5 mL of dilute hydrochloric acid R to 10 mL of reference solution (c), dilute to 25 mL with water R and place in an oven at 70 \u00b0C for 1 h. Dilute 1 mL of this solution to 5 mL with a 27 g\/L solution of dipotassium hydrogen phosphate R previously adjusted to pH 7.0 with phosphoric acid R.<\/p>\n

Reference solution (f): Dilute 2 mL of reference solution (a) to 10 mL with reference solution (e).<\/p>\n

Reference solution (g): Dissolve 1.5 mg of flucloxacillin impurity C CRS in 1 mL of the mobile phase and dilute to 50 mL with the mobile phase.<\/p>\n

Reference solution (h): Dissolve 1 mg of flucloxacillin impurity D CRS in 100 mL of the mobile phase.<\/p>\n

Reference solution (i): Dissolve 1 mg of flucloxacillin impurity E CRS in 100 mL of the mobile phase.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25 m, \u00d8 = 4 mm;<\/p>\n

\u2014 stationary phase: octadecylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n

\u2014 temperature: 40 \u00b0C.<\/p>\n

Mobile phase: Mix 25 volumes of acetonitrile R1 and 75 volumes of a 2.7 g\/L solution of potassium dihydrogen phosphate R previously adjusted to pH 5.0 with dilute sodium hydroxide solution R.<\/p>\n

Flow rate: 1 mL\/min.<\/p>\n

Detection: Spectrophotometer at 225 nm.<\/p>\n

Injection: 20 \u03bcL of test solution (a) and reference solutions (b), (d), (e), (f), (g), (h) and (i).<\/p>\n

Run time: 7 times the retention time of flucloxacillin.<\/p>\n

Identification of impurities: Use the chromatograms obtained with reference solutions (d), (e), (g), (h) and (i) to identify the peaks due to impurities A, B, C, D and E respectively.<\/p>\n

Relative retention: With reference to flucloxacillin (retention time = about 8 min): impurity C = about 0.2; impurity A (isomer 1) = about 0.3; impurity A (isomer 2) = about 0.5; impurity D = about 0.6; impurity B (isomer 1) = about 0.8; impurity B (isomer 2) = about 0.9; impurity E = about 6.<\/p>\n

System suitability Reference solution (f):<\/p>\n

\u2014 resolution: minimum 2.0 between the 2 peak due to impurity B (isomer 2) and the peak due to flucloxacillin.<\/p>\n

Limits:<\/p>\n

\u2014 correction factor: for the calculation of content, multiply the peak area of impurity C by 3.3;<\/p>\n

\u2014 impurity A (sum of the 2 isomers): the sum of the areas of the 2 peaks is not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (2.0 per cent);<\/p>\n

\u2014 impurity B (sum of the 2 isomers): the sum of the areas of the 2 peaks is not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (1.0 per cent);<\/p>\n

\u2014 impurity C: not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (1.0 per cent);<\/p>\n

\u2014 impurities D, E: for each impurity, not more than 0.3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);<\/p>\n

\u2014 any other impurity: for each impurity, not more than 0.3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);<\/p>\n

\u2014 total: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (3.0 per cent);<\/p>\n

\u2014 disregard limit: 0.05 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n

2-Ethylhexanoic acid (2.4.28)<\/h4>\n

Maximum 0.8 per cent m\/m.<\/p>\n

Water (2.5.12)<\/h4>\n

12.0 per cent to 15.0 per cent, determined on 0.100 g.<\/p>\n

ASSAY<\/h2>\n

Liquid chromatography (2.2.29) as described in the test for related substances with the following modifications.<\/p>\n

Injection Test solution (b) and reference solution (a).<\/p>\n

Calculate the percentage content of C38<\/sub>H32<\/sub>Cl2<\/sub>F2<\/sub>MgN6<\/sub>O10<\/sub>S2<\/sub> from the declared content of flucloxacillin sodium CRS, multiplying by 0.9773.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, B, C, D, E.<\/p>\n

\"Flucloxacillin<\/p>\n

A. (4S)-2-[carboxy[[[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carbonyl]amino]methyl]-5,5-dimethylthiazolidine-4- carboxylic acid (penicilloic acids of flucloxacillin),<\/p>\n

\"Flucloxacillin<\/p>\n

B. (2RS,4S)-2-[[[[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carbonyl]amino]methyl]-5,5-dimethylthiazolidine-4- carboxylic acid (penilloic acids of flucloxacillin),<\/p>\n

\"Flucloxacillin<\/p>\n

C. (2S,5R,6R)-6-amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid (6-aminopenicillanic acid),<\/p>\n

\"Flucloxacillin<\/p>\n

D. 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid,<\/p>\n

\"Flucloxacillin<\/p>\n

E. (2S,5R,6R)-6-[[[(2S,5R,6R)-6-[[[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carbonyl]amino]-3,3-dimethyl-7-oxo- 4-thia-1-azabicyclo[3.2.0]hept-2-yl]carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid (6-APA flucloxacillin amide).<\/p>\n","protected":false},"excerpt":{"rendered":"

Flucloxacillin Magnesium (Ph. Eur. monograph 2346) C38H32Cl2F2MgN6O10S2,8H2O\u00a0 \u00a0 \u00a0 \u00a01074\u00a0 \u00a0 \u00a0 58486-36-5 Action and use Penicillin antibacterial. Preparations Flucloxacillin Oral Suspension Co-fluampicil Oral Suspension DEFINITION Magnesium bis[(2S,5R,6R)-6-[[[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate] octahydrate. Semi-synthetic product derived from a fermentation product. Content 95.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, crystalline powder. Solubility…<\/p>\n","protected":false},"author":2,"featured_media":13167,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-13150","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicinal-substances"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13150","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=13150"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13150\/revisions"}],"predecessor-version":[{"id":13170,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13150\/revisions\/13170"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/13167"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=13150"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=13150"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=13150"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}