{"id":14257,"date":"2025-10-15T10:06:29","date_gmt":"2025-10-15T03:06:29","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=14257"},"modified":"2025-10-15T10:06:29","modified_gmt":"2025-10-15T03:06:29","slug":"flucloxacillin-for-injection","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/flucloxacillin-for-injection\/","title":{"rendered":"Flucloxacillin for Injection"},"content":{"rendered":"<p>BP 2025 (Ph. Eur. 11.6 update)<\/p>\n<p><strong>Action and use<\/strong><\/p>\n<p>Penicillin antibacterial.<\/p>\n<h2>DEFINITION<\/h2>\n<p>Flucloxacillin for Injection is a sterile material consisting of Flucloxacillin Sodium Monohydrate with or without excipients. It is supplied in a sealed container.<\/p>\n<p>The contents of the sealed container comply with the requirements for Powders for Injections or Infusions stated under Parenteral Preparations and with the following requirements.<\/p>\n<p><strong>Content of flucloxacillin, C<sub>19<\/sub>H<sub>17<\/sub>ClFN<sub>3<\/sub>O<sub>5<\/sub>S<\/strong><\/p>\n<p>95.0 to 105.0% of the stated amount.<\/p>\n<h2>IDENTIFICATION<\/h2>\n<p>A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of flucloxacillin sodium (RS 145).<\/p>\n<p>B. Yield reaction B characteristic of sodium salts, Appendix VI.<\/p>\n<h2>TESTS<\/h2>\n<p><strong>Acidity or alkalinity<\/strong><\/p>\n<p>pH of a solution containing the equivalent of 10% w\/v of flucloxacillin, 5.0 to 7.0, Appendix V L.<\/p>\n<p><strong>Related substances<\/strong><\/p>\n<p>Carry out the method for liquid chromatography, Appendix III D, using the following solutions in 50% v\/v acetonitrile.<\/p>\n<p>Prepare the solutions protected from light.<\/p>\n<p>(1) Disperse a quantity of the contents of the sealed container containing the equivalent of 0.1 g of flucloxacillin in 50% v\/v of acetonitrile and dilute to 100 mL.<\/p>\n<p>(2) Dilute 1 volume of solution (1) to 100 volumes.<\/p>\n<p>(3) 0.001% w\/v of flucloxacillin impurity D EPCRS and 0.1% w\/v of flucloxacillin sodium BPCRS.<\/p>\n<p>(4) 0.1% w\/v of flucloxacillin for peak identification EPCRS.<\/p>\n<p>(5) Dilute 1 volume of solution (2) to 10 volumes.<\/p>\n<h3>CHROMATOGRAPHIC CONDITIONS<\/h3>\n<p>(a) Use a stainless steel column (25 cm \u00d7 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 \u03bcm) (Zorbax SB-C18 is suitable).<br \/>\n(b) Use gradient elution and the mobile phase described below.<br \/>\n(c) Use a flow rate of 1.5 mL per minute.<br \/>\n(d) Use a column temperature of 40\u00b0.<br \/>\n(e) Use a detection wavelength of 225 nm.<br \/>\n(f) Inject 10 \u03bcL of each solution.<\/p>\n<h3>MOBILE PHASE<\/h3>\n<p><em>Mobile phase A<\/em> 0.118% w\/v sodium hexanesulfonate monohydrate for ion-pair chromatography in a mixture of 0.8 volumes of concentrated ammonia and 1000 volumes of water for chromatography. Adjust the pH of the resulting solution to pH 2.9 \u00b1 0.1 with orthophosphoric acid.<\/p>\n<p><em>Mobile phase B<\/em> acetonitrile R1.<\/p>\n<table style=\"border-collapse: collapse; width: 100%; height: 105px;\">\n<tbody>\n<tr style=\"height: 21px;\">\n<td style=\"width: 25%; height: 21px;\">Time (Minutes)<\/td>\n<td style=\"width: 25%; height: 21px;\">Mobile phase A (% v\/v)<\/td>\n<td style=\"width: 25%; height: 21px;\">Mobile phase B (% v\/v)<\/td>\n<td style=\"width: 25%; height: 21px;\">Comment<\/td>\n<\/tr>\n<tr style=\"height: 21px;\">\n<td style=\"width: 25%; height: 21px;\">0-30<\/td>\n<td style=\"width: 25%; height: 21px;\">80\u219245<\/td>\n<td style=\"width: 25%; height: 21px;\">20\u219255<\/td>\n<td style=\"width: 25%; height: 21px;\">linear gradient<\/td>\n<\/tr>\n<tr style=\"height: 21px;\">\n<td style=\"width: 25%; height: 21px;\">30-35<\/td>\n<td style=\"width: 25%; height: 21px;\">45\u219235<\/td>\n<td style=\"width: 25%; height: 21px;\">55\u219265<\/td>\n<td style=\"width: 25%; height: 21px;\">linear gradient<\/td>\n<\/tr>\n<tr style=\"height: 21px;\">\n<td style=\"width: 25%; height: 21px;\">35-40<\/td>\n<td style=\"width: 25%; height: 21px;\">35\u219280<\/td>\n<td style=\"width: 25%; height: 21px;\">65\u219220<\/td>\n<td style=\"width: 25%; height: 21px;\">linear gradient<\/td>\n<\/tr>\n<tr style=\"height: 21px;\">\n<td style=\"width: 25%; height: 21px;\">40-45<\/td>\n<td style=\"width: 25%; height: 21px;\">80<\/td>\n<td style=\"width: 25%; height: 21px;\">20<\/td>\n<td style=\"width: 25%; height: 21px;\">e-equilibration<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to flucloxacillin (retention time about 18 minutes) are: impurity C, about 0.1; 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 0.75; impurity B (isomer 2), about 0.8; impurity D, about 0.9; impurity H, about 1.2; impurity E, about 1.25; impurity I, about 1.35; impurity J, about 1.55 and impurity K, about 1.6.<\/p>\n<h3>SYSTEM SUITABILITY<\/h3>\n<p>The test is not valid unless:<\/p>\n<p>in the chromatogram obtained with solution (3), the resolution between impurity D and flucloxacillin is at least 1.5.<\/p>\n<p>in the chromatogram obtained with solution (5), the signal-to-noise ratio of the principal peak is at least 40.<\/p>\n<h3>LIMITS<\/h3>\n<p>Identify any peak corresponding to impurities B and C in the chromatogram obtained with solution (1), using the chromatogram obtained with solution (4), and multiply the area of these peaks by a correction factor of 1.3 and 4.2 respectively.<br \/>\nIn the chromatogram obtained with solution (1):<br \/>\nthe sum of the areas of any peaks corresponding to impurity A is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (2%);<br \/>\nthe sum of the areas of any peaks corresponding to impurity B is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%);<br \/>\nthe area of any peaks corresponding to impurity C or E is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);<br \/>\nthe area of any peak corresponding to impurity H is not greater than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);<br \/>\nthe area of any peaks corresponding to impurity F, I, J or K is not greater than 0.4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.4%);<br \/>\nthe area of any peaks corresponding to impurity D or G is not greater than 0.3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);<br \/>\nthe area of any other secondary peak is not greater than 0.2 times the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);<\/p>\n<p>the sum of the areas of all secondary peaks is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (5.0%).<br \/>\nDisregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (5) (0.1%).<\/p>\n<p><strong>Bacterial endotoxins<\/strong><\/p>\n<p>Carry out the test for bacterial endotoxins, Appendix XIV C. Dissolve the contents of the sealed container in water BET to give a solution containing the equivalent of 9 mg of flucloxacillin per mL (solution A). The endotoxin limit concentration of solution A is less than 0.35 IU per mL.<\/p>\n<h2>ASSAY<\/h2>\n<p>Determine the weight of the contents of 10 containers as described in the test for uniformity of weight, Appendix XII C1, Powders for Parenteral Administration.<br \/>\nCarry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in 50% v\/v of acetonitrile.<br \/>\n(1) Disperse a quantity of mixed contents of the 10 containers, containing the equivalent of 0.5 g of flucloxacillin in 50% v\/v of acetonitrile and dilute to 200 mL. Dilute 1 volume of the resulting solution to 25 volumes.<br \/>\n(2) 0.011% w\/v of flucloxacillin sodium BPCRS.<br \/>\n(3) 0.0001% w\/v of flucloxacillin impurity D EPCRS and 0.01% w\/v of flucloxacillin sodium BPCRS.<\/p>\n<h3>CHROMATOGRAPHIC CONDITIONS<\/h3>\n<p>(a) Use a stainless steel column (25 cm \u00d7 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 \u03bcm)<br \/>\n(Zorbax SB-C18 is suitable).<br \/>\n(b) Use gradient elution and the mobile phase described below.<br \/>\n(c) Use a flow rate of 1.8 mL per minute.<br \/>\n(d) Use a column temperature of 40\u00b0.<br \/>\n(e) Use a detection wavelength of 225 nm.<br \/>\n(f) Inject 10 \u03bcL of each solution.<\/p>\n<h3>MOBILE PHASE<\/h3>\n<p><em>Mobile phase A<\/em> 0.118% w\/v sodium hexanesulfonate monohydrate for ion-pair chromatography in a mixture of 0.8 volumes of concentrated ammonia and 1000 volumes of water. Adjust the pH of the resulting solution to pH 3.1 \u00b1 0.1 with orthophosphoric acid.<\/p>\n<p><em>Mobile phase B<\/em> acetonitrile R1.<\/p>\n<table style=\"border-collapse: collapse; width: 100%; height: 105px;\">\n<tbody>\n<tr style=\"height: 21px;\">\n<td style=\"width: 25%; height: 21px;\">Time (Minutes)<\/td>\n<td style=\"width: 25%; height: 21px;\">Mobile phase A (% v\/v)<\/td>\n<td style=\"width: 25%; height: 21px;\">Mobile phase B (% v\/v)<\/td>\n<td style=\"width: 25%; height: 21px;\">Comment<\/td>\n<\/tr>\n<tr style=\"height: 21px;\">\n<td style=\"width: 25%; height: 21px;\">0-8<\/td>\n<td style=\"width: 25%; height: 21px;\">65\u219241<\/td>\n<td style=\"width: 25%; height: 21px;\">35\u219259<\/td>\n<td style=\"width: 25%; height: 21px;\">linear gradient<\/td>\n<\/tr>\n<tr style=\"height: 21px;\">\n<td style=\"width: 25%; height: 21px;\">8-12<\/td>\n<td style=\"width: 25%; height: 21px;\">41\u219265<\/td>\n<td style=\"width: 25%; height: 21px;\">59\u219235<\/td>\n<td style=\"width: 25%; height: 21px;\">linear gradient<\/td>\n<\/tr>\n<tr style=\"height: 21px;\">\n<td style=\"width: 25%; height: 21px;\">12-18<\/td>\n<td style=\"width: 25%; height: 21px;\">65<\/td>\n<td style=\"width: 25%; height: 21px;\">35<\/td>\n<td style=\"width: 25%; height: 21px;\">re-equilibration<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<h3>SYSTEM SUITABILITY<\/h3>\n<p>The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between impurity D and flucloxacillin is at least 1.5.<\/p>\n<h3>DETERMINATION OF CONTENT<\/h3>\n<p>Calculate the content of C<sub>19<\/sub>H<sub>17<\/sub>ClFN<sub>3<\/sub>O<sub>5<\/sub>S in a container of average content weight using the declared content of C<sub>19<\/sub>H<sub>16<\/sub>ClFN<sub>3<\/sub>NaO<sub>5<\/sub>S\u00a0in flucloxacillin sodium BPCRS. Each mg of C<sub>19<\/sub>H<sub>16<\/sub>ClFN<sub>3<\/sub>NaO<sub>5<\/sub>S is equivalent to 0.9538 mg of C<sub>19<\/sub>H<sub>17<\/sub>ClFN<sub>3<\/sub>O<sub>5<\/sub>S .<\/p>\n<h2>LABELLING<\/h2>\n<p>The quantity of active ingredient is stated in terms of the equivalent amount of flucloxacillin.<\/p>\n<h2>IMPURITIES<\/h2>\n<p>The impurities limited by the requirements of this monograph include those listed under Flucloxacillin Sodium Monohydrate.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>BP 2025 (Ph. Eur. 11.6 update) Action and use Penicillin antibacterial. DEFINITION Flucloxacillin for Injection is a sterile material consisting of Flucloxacillin Sodium Monohydrate with or without excipients. It is supplied in a sealed container. The contents of the sealed container comply with the requirements for Powders for Injections or Infusions stated under Parenteral Preparations&#8230;<\/p>\n","protected":false},"author":5,"featured_media":14335,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-14257","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-formulated-preparations-specific-monographs"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/14257","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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=14257"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/14257\/revisions"}],"predecessor-version":[{"id":14342,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/14257\/revisions\/14342"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/14335"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=14257"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=14257"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=14257"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}