﻿{"id":3491,"date":"2025-09-24T13:49:08","date_gmt":"2025-09-24T06:49:08","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=3491"},"modified":"2025-11-15T12:55:21","modified_gmt":"2025-11-15T05:55:21","slug":"benzalkonium-chloride-solution","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/benzalkonium-chloride-solution\/","title":{"rendered":"Benzalkonium Chloride Solution"},"content":{"rendered":"<p>(Ph. Eur. monograph 0371)<\/p>\n<p><strong>Action and use<\/strong><\/p>\n<p>Antiseptic.<\/p>\n<h2>DEFINITION<\/h2>\n<p>Aqueous solution of a mixture of alkylbenzyldimethylammonium chlorides, the alkyl groups mainly having chain lengths of C<sub>12<\/sub>, C<sub>14<\/sub> and C<sub>16<\/sub>.<\/p>\n<h3>Content<\/h3>\n<p>475 g\/L to 525 g\/L of alkylbenzyldimethylammonium chlorides, calculated using the average relative molecular mass (see Tests). The solution may contain ethanol (96 per cent).<\/p>\n<h2>CHARACTERS<\/h2>\n<h3>Appearance<\/h3>\n<p>Clear, colourless or slightly yellowish liquid.<\/p>\n<h3>Solubility<\/h3>\n<p>Miscible with water and with ethanol (96 per cent).<\/p>\n<p>It froths copiously when shaken.<\/p>\n<h2>IDENTIFICATION<\/h2>\n<p>First identification: B, E.<\/p>\n<p>Second identification: A, C, D, E.<\/p>\n<p>A. Ultraviolet and visible absorption spectrophotometry (2.2.25).<\/p>\n<p>Test solution: Dilute 0.3 mL to 100.0 mL with water R.<\/p>\n<p>Spectral range: 220-350 nm.<\/p>\n<p>Absorption maxima: At 257 nm, 263 nm and 269 nm.<\/p>\n<p>Shoulder: At about 250 nm.<\/p>\n<p>B. Examine the chromatograms obtained in the test for average relative molecular mass and ratio of alkyl components.<\/p>\n<p>Results: The principal peaks in the chromatogram obtained with the test solution are similar in retention time to the principal peaks in the chromatogram obtained with the reference solution.<\/p>\n<p>C. To 0.05 mL add 2 mL of water R, 0.1 mL of glacial acetic acid R and, dropwise, 1 mL of sodium tetraphenylborate solution R. A white precipitate is formed. Filter. Dissolve the precipitate in a mixture of 1 mL of acetone R and 5 mL of ethanol (96 per cent) R, heating to not more than 70 \u00b0C. Add water R dropwise to the warm solution until a slight opalescence forms. Heat gently until the solution is clear and allow to cool. White crystals separate. Filter, wash with 3 quantities, each of 10 mL, of water R and dry in vacuo (2.2.32) at a temperature not exceeding 50 \u00b0C. The crystals melt (2.2.14) at 127 \u00b0C to 133 \u00b0C.<\/p>\n<p>D. To 5 mL of dilute sodium hydroxide solution R add 0.1 mL of bromophenol blue solution R1 and 5 mL of methylene chloride R and shake. The methylene chloride layer is colourless. Add 0.05 mL of the solution to be examined and shake. The methylene chloride layer becomes blue.<\/p>\n<p>E. To 0.05 mL add 1 mL of dilute nitric acid R. A white precipitate is formed which dissolves on the addition of 5 mL of ethanol (96 per cent) R. The solution gives reaction (a) of chlorides (2.3.1).<\/p>\n<h2>TESTS<\/h2>\n<h3>Solution S<\/h3>\n<p>Dilute 2.0 g to 100 mL with carbon dioxide-free water R.<\/p>\n<h3>Appearance of solution<\/h3>\n<p>Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y<sub>6<\/sub> (2.2.2, Method II).<\/p>\n<h3>Acidity or alkalinity<\/h3>\n<p>To 50 mL of solution S add 0.1 mL of bromocresol purple solution R. Not more than 0.1 mL of 0.1 M hydrochloric acid or 0.1 M sodium hydroxide is required to change the colour of the indicator.<\/p>\n<h3>Average relative molecular mass and ratio of alkyl components<\/h3>\n<p>Liquid chromatography (2.2.29).<\/p>\n<p>Test solution: Determine the density (2.2.5) of the solution to be examined. Dilute a quantity of the solution to be examined equivalent to about 0.400 g of benzalkonium chloride to 100.0 mL with water R.<\/p>\n<p>Reference solution: Dissolve the contents of a vial of benzalkonium chloride for system suitability CRS in 5 mL of water R.<\/p>\n<p>Column:<\/p>\n<p>\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n<p>\u2014 stationary phase: end-capped cyanosilyl silica gel for chromatography R (5 \u03bcm).<\/p>\n<p>Mobile phase: Mix 45 volumes of acetonitrile R and 55 volumes of a 13.6 g\/L solution of sodium acetate R previously adjusted to pH 5.0 with glacial acetic acid R.<\/p>\n<p>Flow rate: 2.0 mL\/min.<\/p>\n<p>Detection: Spectrophotometer at 254 nm.<\/p>\n<p>Injection: 10 \u03bcL.<\/p>\n<p>Identification of homologues: Use the chromatogram supplied with benzalkonium chloride for system suitability CRS and the chromatogram obtained with the reference solution to identify the peaks due to homologues C<sub>12<\/sub>, C<sub>14<\/sub> and C<sub>16<\/sub>.<\/p>\n<p>Relative retention: With reference to C<sub>12<\/sub> homologue (retention time = about 6 min): C<sub>14<\/sub> homologue = about 1.3; C<sub>16<\/sub> homologue = about 1.7.<\/p>\n<p>System suitability: Reference solution:<\/p>\n<p>\u2014 resolution: minimum 1.5 between the peaks due to the C12 and C14 homologues.<\/p>\n<p>Calculate the average relative molecular mass of the sample by summing the products for each homologue, using the following expression:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3523\" src=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/09\/Benzalkonium-Chloride-Solution-1.jpg\" alt=\"Benzalkonium Chloride Solution\" width=\"250\" height=\"100\" \/><\/p>\n<p>A = area of the peak due to the given homologue in the chromatogram obtained with the test solution;<\/p>\n<p>B = sum of the areas of the peaks due to all homologues in the chromatogram obtained with the test solution;<\/p>\n<p>W = relative molecular mass for the given homologue: 340, 368 and 396 for the C<sub>12<\/sub>, C<sub>14<\/sub> and C<sub>16<\/sub> homologues, respectively.<\/p>\n<p>Calculate the percentage of each homologue, using the following expression:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3524\" src=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/09\/Benzalkonium-Chloride-Solution-2.jpg\" alt=\"Benzalkonium Chloride Solution\" width=\"250\" height=\"100\" \/><\/p>\n<p>C = product of the relative molecular mass of the given homologue and the area of the corresponding peak in the chromatogram obtained with the test solution;<\/p>\n<p>D = sum of the C values for all homologues quantified.<\/p>\n<p>Limits:<\/p>\n<p>\u2014 C<sub>12<\/sub> homologue: minimum 40 per cent;<\/p>\n<p>\u2014 C<sub>14<\/sub> homologue: minimum 20 per cent;<\/p>\n<p>\u2014 sum of C<sub>12 <\/sub>and C<sub>14<\/sub> homologues: minimum 70 per cent.<\/p>\n<h3>Impurities A, B and C<\/h3>\n<p>Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n<p>Test solution Determine the density (2.2.5) of the solution to be examined. Dilute a quantity of the solution to be examined equivalent to 2.5 g of benzalkonium chloride to 50.0 mL with methanol R.<\/p>\n<p>Reference solution (a): Dissolve 25.0 mg of benzyl alcohol CRS (impurity A) in methanol R and dilute to 100.0 mL with the same solvent.<\/p>\n<p>Reference solution (b): Dissolve 75.0 mg of benzaldehyde CRS (impurity B) in methanol R and dilute to 100.0 mL with the same solvent. Dilute 1.0 mL of this solution to 10.0 mL with methanol R.<\/p>\n<p>Reference solution (c:) Dilute 1 mL of reference solution (a) to 10 mL with methanol R.<\/p>\n<p>Column:<\/p>\n<p>\u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n<p>\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n<p>\u2014 temperature: 30 \u00b0C.<\/p>\n<p>Mobile phase:<\/p>\n<p>\u2014 mobile phase A: dissolve 1.09 g of sodium hexanesulfonate R and 6.9 g of sodium dihydrogen phosphate monohydrate R in water for chromatography R; adjust to pH 3.5 with phosphoric acid R and dilute to 1000 mL with the same solvent;<\/p>\n<p>\u2014 mobile phase B: methanol R2;<\/p>\n<table style=\"border-collapse: collapse; width: 100%;\">\n<tbody>\n<tr>\n<td style=\"width: 33.3333%; text-align: center;\"><strong>Time<\/strong><br \/>\n<strong>(min)<\/strong><\/td>\n<td style=\"width: 33.3333%; text-align: center;\"><strong>Mobile phase A<\/strong><br \/>\n<strong>(per cent V\/V)<\/strong><\/td>\n<td style=\"width: 33.3333%; text-align: center;\"><strong>Mobile phase B<\/strong><br \/>\n<strong>(per cent V\/V)<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"width: 33.3333%; text-align: center;\">0 &#8211; 10<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">80<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">20<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 33.3333%; text-align: center;\">10 &#8211; 14<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">80 \u2192 50<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">20 \u2192 50<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 33.3333%; text-align: center;\">14 &#8211; 35<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">50<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">50<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 33.3333%; text-align: center;\">35 &#8211; 36<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">\u00a050 \u2192 20<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">50 \u2192 80<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 33.3333%; text-align: center;\">36 &#8211; 55<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">20<\/td>\n<td style=\"width: 33.3333%; text-align: center;\">80<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>Flow rate:1.0 mL\/min.<\/p>\n<p>Detection: Spectrophotometer at 210 nm for impurities A and C, and at 257 nm for impurity B.<\/p>\n<p>Injection: 20 \u03bcL.<\/p>\n<p>Relative retention: With reference to impurity A (retention time = about 10 min): impurity B = about 1.3; impurity C = about 2.4.<\/p>\n<p>System suitability: At 210 nm:<\/p>\n<p>\u2014 signal-to-noise ratio: minimum 10 for the principal peak in the chromatogram obtained with reference solution (c);<\/p>\n<p>\u2014 symmetry factor: minimum 0.6 for the peak due to impurity A in the chromatogram obtained with reference solution (a).<\/p>\n<p>Limits:<\/p>\n<p>\u2014 correction factor: for the calculation of content, multiply the peak area of impurity C by 1.3;<\/p>\n<p>\u2014 impurity A: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (a) (0.5 per cent);<\/p>\n<p>\u2014 impurity B: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (b) (0.15 per cent);<\/p>\n<p>\u2014 impurity C: not more than 0.1 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n<h3>Amines and amine salts<\/h3>\n<p>Mix 10.0 g, while heating, with 20 mL of a mixture of 3 volumes of 1 M hydrochloric acid and 97 volumes of methanol R and add 100 mL of 2-propanol R. Pass a stream of nitrogen R slowly through the solution. Titrate with up to 12.0 mL of 0.1 M tetrabutylammonium hydroxide and record the potentiometric titration curve (2.2.20). If the curve shows 2 points of inflexion, the volume of titrant added between the 2 points is not greater than 5.0 mL. If the curve shows no point of inflexion, the solution to be examined does not comply with the test. If the curve shows 1 point of inflexion, repeat the test but add 3.0 mL of a 25.0 g\/L solution of dimethyldecylamine R in 2-propanol R before the titration. If the titration curve after the addition of 12.0 mL of the titrant shows only 1 point of inflexion, the solution to be examined does not comply with the test.<\/p>\n<h4>Sulfated ash (2.4.14)<\/h4>\n<p>Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n<h2>ASSAY<\/h2>\n<p>Determine the density (2.2.5) of the solution to be examined. Dilute 4.00 g to 100.0 mL with water R. Transfer 25.0 mL of the solution to a separating funnel, add 25 mL of methylene chloride R, 10 mL of 0.1 M sodium hydroxide and 10.0 mL of a freshly prepared 50 g\/L solution of potassium iodide R. Shake well, allow to separate and discard the methylene chloride layer. Shake the aqueous layer with 3 quantities, each of 10 mL, of methylene chloride R and discard the methylene chloride layers. To the aqueous layer add 40 mL of hydrochloric acid R, allow to cool and titrate with 0.05 M potassium iodate until the deep-brown colour is almost discharged. Add 5 mL of methylene chloride R and continue the titration, shaking vigorously, until the methylene chloride layer no longer changes colour. Carry out a blank titration on a mixture of 10.0 mL of the freshly prepared 50 g\/L solution of potassium iodide R, 20 mL of water R and 40 mL of hydrochloric acid R.<\/p>\n<p>1 mL of 0.05 M potassium iodate is equivalent to mg of benzalkonium chloride where x is the average relative molecular mass of the sample.<\/p>\n<h2>LABELLING<\/h2>\n<p>The label states the content of ethanol (96 per cent), if any.<\/p>\n<h2>IMPURITIES<\/h2>\n<p>Specified impurities A, B, C.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3528\" src=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/09\/Benzalkonium-Chloride-Solution-A.jpg\" alt=\"Benzalkonium Chloride Solution\" width=\"300\" height=\"200\" \/><\/p>\n<p>A. benzyl alcohol,<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3527\" src=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/09\/Benzalkonium-Chloride-Solution-B.jpg\" alt=\"Benzalkonium Chloride Solution\" width=\"300\" height=\"200\" \/><\/p>\n<p>B. benzaldehyde,<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3526\" src=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/09\/Benzalkonium-Chloride-Solution-C.jpg\" alt=\"Benzalkonium Chloride Solution\" width=\"300\" height=\"200\" \/><\/p>\n<p>C. (chloromethyl)benzene.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>(Ph. Eur. monograph 0371) Action and use Antiseptic. DEFINITION Aqueous solution of a mixture of alkylbenzyldimethylammonium chlorides, the alkyl groups mainly having chain lengths of C12, C14 and C16. Content 475 g\/L to 525 g\/L of alkylbenzyldimethylammonium chlorides, calculated using the average relative molecular mass (see Tests). The solution may contain ethanol (96 per cent)&#8230;.<\/p>\n","protected":false},"author":2,"featured_media":3529,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-3491","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\/3491","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=3491"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/3491\/revisions"}],"predecessor-version":[{"id":5227,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/3491\/revisions\/5227"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/3529"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=3491"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=3491"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=3491"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}