{"id":11876,"date":"2025-10-10T10:22:39","date_gmt":"2025-10-10T03:22:39","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=11876"},"modified":"2025-11-15T15:38:36","modified_gmt":"2025-11-15T08:38:36","slug":"flucloxacillin-sodium-monohydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/flucloxacillin-sodium-monohydrate\/","title":{"rendered":"Flucloxacillin Sodium Monohydrate"},"content":{"rendered":"

Flucloxacillin Sodium<\/p>\n

(Ph. Eur. monograph 0668)<\/p>\n

C19<\/sub>H16<\/sub>ClFN3<\/sub>NaO5<\/sub>S,H2<\/sub>O 493.9 34214-51-2<\/p>\n

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

Penicillin antibacterial.<\/p>\n

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

Flucloxacillin Capsules<\/p>\n

Co-fluampicil Capsules<\/p>\n

Flucloxacillin Infusion<\/p>\n

Flucloxacillin Injection<\/p>\n

Flucloxacillin Oral Solution<\/p>\n

DEFINITION<\/h2>\n

Sodium (2S,5R,6R)-6-[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate monohydrate.<\/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

PRODUCTION<\/h2>\n

The manufacturing process is evaluated to determine the potential presence of N,N-dimethylaniline. Where necessary, the manufacturing process is validated to demonstrate that the flucloxacillin sodium monohydrate complies with the following test:<\/p>\n

N,N-Dimethylaniline (2.4.26, Method B)<\/p>\n

Maximum 20 ppm.<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Solubility<\/h3>\n

Freely soluble in water and in methanol, soluble in ethanol (96 per cent), practically insoluble in dichloromethane.<\/p>\n

IDENTIFICATION<\/h2>\n

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

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

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

Comparison flucloxacillin sodium 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 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 to iodine vapour until the spots appear and examine in daylight.<\/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. Place about 2 mg in a test-tube about 150 mm long and 15 mm in diameter. Moisten with 0.05 mL of water R and add 2 mL of sulfuric acid-formaldehyde reagent R. Mix the contents of the tube by swirling; the colour of the solution is slightly greenish-yellow. Place the test-tube in a water-bath for 1 min; the solution becomes yellow.<\/p>\n

D. It gives reaction (a) of sodium (2.3.1).<\/p>\n

TESTS<\/h2>\n

Solution S<\/h3>\n

Dissolve 2.50 g in carbon dioxide-free water R and dilute to 25.0 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n

Solution S is clear (2.2.1) and its absorbance (2.2.25) at 430 nm is not greater than 0.04.<\/p>\n

pH (2.2.3)<\/p>\n

5.0 to 7.0 for solution S.<\/p>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29).<\/p>\n

Solvent mixture water R, acetonitrile R (50:50 V\/V).<\/p>\n

Test solution (a): Dissolve 0.100 g of the substance to be examined in the solvent mixture and dilute to 100.0 mL with the solvent mixture. Protect the solution from light.<\/p>\n

Test solution (b): Dilute 2.0 mL of test solution (a) to 20.0 mL with the solvent mixture.<\/p>\n

Reference solution (a): Dissolve 25.0 mg of flucloxacillin sodium CRS in the solvent mixture and dilute to 25.0 mL with the solvent mixture. Protect the solution from light.<\/p>\n

Reference solution (b): Dilute 2.0 mL of reference solution (a) to 20.0 mL with the solvent mixture.<\/p>\n

Reference solution (c): Dilute 1.0 mL of reference solution (a) to 100.0 mL with the solvent mixture.<\/p>\n

Reference solution (d): Dissolve 5 mg of flucloxacillin for peak identification CRS (containing impurities A, B, C, D, E, F, G, H, I, J and K) in the solvent mixture and dilute to 5 mL with the solvent mixture. Protect the solution from light.<\/p>\n

Reference solution (e): Dissolve 5 mg of flucloxacillin impurity D CRS in the solvent mixture and dilute to 50 mL with the solvent mixture. Protect the solution from light.<\/p>\n

Reference solution (f): Dissolve 20 mg of flucloxacillin sodium CRS in the solvent mixture, add 2 mL of reference solution (e) and dilute to 20 mL with the solvent mixture. Protect the solution from light.<\/p>\n

Reference solution (g): Dilute 2 mL of reference solution (f) to 20.0 mL with the solvent mixture.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n

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

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

Mobile phase:<\/p>\n

\u2014 mobile phase A: dissolve 1.18 g of sodium hexanesulfonate monohydrate for ion-pair chromatography R in water for chromatography R, add 0.8 mL of concentrated ammonia R1 and dilute to 1000 mL with water for chromatography R; adjust to pH 2.8-3.0 with concentrated phosphoric acid R;<\/p>\n

\u2014 mobile phase B: acetonitrile for chromatography R;<\/p>\n\n\n\n\n\n
Time
\n(min)<\/td>\n		Mobile phase A
\n(per cent V\/V)<\/td>\n		Mobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 30<\/td>\n80 \u2192 45<\/td>\n\u00a020 \u2192 55<\/td>\n<\/tr>\n
30 – 35<\/td>\n\u00a045 \u2192 35<\/td>\n\u00a055 \u2192 65<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Flow rate 1.5 mL\/min.<\/p>\n

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

Injection 10 \u03bcL of test solution (a) and reference solutions (c), (d) and (f).<\/p>\n

Identification of impurities: Use the chromatogram supplied with flucloxacillin for peak identification CRS and the chromatogram obtained with reference solution (d) to identify the peaks due to impurities A, B, C, D, E, F, G, H, I, J and K.<\/p>\n

Relative retention: With reference to flucloxacillin (retention time = about 19 min): impurity C = about 0.09; impurity A (isomer 1) = about 0.48; impurity A (isomer 2) = about 0.50; impurity F = about 0.55; impurity G = about 0.65; impurity B (isomer 1) = about 0.76; impurity B (isomer 2) = about 0.79; impurity D = about 0.94; impurity H = about 1.22; impurity E = about 1.26; impurity I = about 1.35; impurity J = about 1.57; impurity K = about 1.59.<\/p>\n

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

\u2014 resolution: minimum 1.5 between the peaks due to impurity D and flucloxacillin.<\/p>\n

Calculation of percentage contents:<\/p>\n

\u2014 for each impurity, use the concentration of flucloxacillin sodium monohydrate in reference solution (c);<\/p>\n

\u2014 correction factor: multiply the peak areas of the following impurities by the corresponding correction factor:<\/p>\n

impurity B = 1.3; impurity C = 4.2.<\/p>\n

Limits:<\/p>\n

\u2014 impurity A (sum of the 2 isomers): maximum 2.0 per cent;<\/p>\n

\u2014 impurity B (sum of the 2 isomers): maximum 1.5 per cent;<\/p>\n

\u2014 impurities C, E: for each impurity, maximum 1.0 per cent;<\/p>\n

\u2014 impurity H: maximum 0.5 per cent;<\/p>\n

\u2014 impurities F, I, J, K: for each impurity, maximum 0.4 per cent;<\/p>\n

\u2014 impurities D, G: for each impurity, maximum 0.3 per cent;<\/p>\n

\u2014 any other impurity: for each impurity, maximum 0.2 per cent;<\/p>\n

\u2014 total: maximum 5.0 per cent;<\/p>\n

\u2014 reporting threshold: 0.05 per cent.<\/p>\n

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

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

Water (2.5.12)<\/h4>\n

3.0 per cent to 4.5 per cent, determined on 0.300 g.<\/p>\n

Pyrogens (2.6.8)<\/h4>\n

If intended for use in the manufacture of parenteral preparations without a further appropriate procedure for the removal of pyrogens, it complies with the test. Inject per kilogram of the rabbit’s mass 1 mL of a solution in water for injections R containing 20 mg of the substance to be examined per millilitre.<\/p>\n

ASSAY<\/h2>\n

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

Mobile phase:<\/p>\n

\u2014 mobile phase A: dissolve 1.18 g of sodium hexanesulfonate monohydrate for ion-pair chromatography R in water for chromatography R, add 0.8 mL of concentrated ammonia R1 and dilute to 1000 mL with water for chromatography R; adjust to pH 3.0-3.2 with concentrated phosphoric acid R;<\/p>\n

\u2014 mobile phase B: acetonitrile for chromatography R;<\/p>\n\n\n\n\n
Time
\n(min)<\/td>\n		Mobile phase A
\n(per cent V\/V)<\/td>\n		Mobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 8<\/td>\n\u00a065 \u2192 41<\/td>\n\u00a035 \u2192 59<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Flow rate 1.8 mL\/min.<\/p>\n

Injection: Test solution (b) and reference solutions (b) and (g).<\/p>\n

Relative retention: With reference to flucloxacillin (retention time = about 5.3 min): impurity D = about 1.04.<\/p>\n

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

\u2014 resolution: minimum 1.5 between the peaks due to impurity D and flucloxacillin.<\/p>\n

Calculate the percentage content of C19<\/sub>H16<\/sub>ClFN3<\/sub>NaO5<\/sub>S using the chromatogram obtained with reference solution (b) and taking into account the assigned content of flucloxacillin sodium CRS.<\/p>\n

STORAGE<\/h2>\n

In an airtight container, at a temperature not exceeding 25 \u00b0C. If the substance is sterile, the container is also sterile and tamper-evident.<\/p>\n

LABELLING<\/h2>\n

The label states, where applicable, that the substance is suitable for use in the manufacture of parenteral preparations.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, B, C, D, E, F, G, H, I, J, K.<\/p>\n

\"Flucloxacillin<\/p>\n

A. (2\u039e,4S)-2-[(\u039e)-carboxy[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid (penicilloic acids of flucloxacillin),<\/p>\n

\"Flucloxacillin<\/p>\n

B. (2\u039e,4S)-2-[[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]methyl]-5,5-dimethyl-1,3-thiazolidine-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-methyl-1,2-oxazole-4-carboxylic acid,<\/p>\n

\"Flucloxacillin<\/p>\n

E. (2S,5R,6R)-6-[(2S,5R,6R)-6-[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-amido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid (6-APA flucloxacillin amide),<\/p>\n

\"Flucloxacillin<\/p>\n

F. [3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]acetic acid,<\/p>\n

\"Flucloxacillin<\/p>\n

G. (2\u039e,4S)-3-acetyl-2-[(\u039e)-carboxy[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid,<\/p>\n

\"Flucloxacillin<\/p>\n

H. (2\u039e,4S)-2-[(\u039e)-carboxy[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]methyl]-3-[[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]acetyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid,<\/p>\n

\"Flucloxacillin<\/p>\n

I. (2\u039e)-2-[[(Z)-[2-[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]-5-oxo-1,3-oxazol-4(5H)-ylidene]methyl]amino]-3-methyl-3-sulfanylbutanoic acid,<\/p>\n

\"Flucloxacillin<\/p>\n

J. (2S,5R,6R)-6-[(2\u039e)-2-[(2\u039e,4S)-4-carboxy-5,5-dimethyl-1,3-thiazolidin-2-yl]-2-[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid,<\/p>\n

K. unknown structure.<\/p>\n","protected":false},"excerpt":{"rendered":"

Flucloxacillin Sodium (Ph. Eur. monograph 0668) C19H16ClFN3NaO5S,H2O 493.9 34214-51-2 Action and use Penicillin antibacterial. Preparations Flucloxacillin Capsules Co-fluampicil Capsules Flucloxacillin Infusion Flucloxacillin Injection Flucloxacillin Oral Solution DEFINITION Sodium (2S,5R,6R)-6-[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-amido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate monohydrate. Semi-synthetic product derived from a fermentation product. Content 95.0 per cent to 102.0 per cent (anhydrous substance). PRODUCTION The manufacturing process is evaluated to determine…<\/p>\n","protected":false},"author":3,"featured_media":11899,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-11876","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\/11876","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=11876"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/11876\/revisions"}],"predecessor-version":[{"id":11902,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/11876\/revisions\/11902"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/11899"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=11876"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=11876"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=11876"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}