{"id":17767,"date":"2025-10-22T15:56:20","date_gmt":"2025-10-22T08:56:20","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=17767"},"modified":"2025-10-22T15:57:16","modified_gmt":"2025-10-22T08:57:16","slug":"levodropropizine","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/levodropropizine\/","title":{"rendered":"Levodropropizine"},"content":{"rendered":"<p><em>(Ph. Eur. monograph 1535)<\/em><\/p>\n<p>C<sub>13<\/sub>H<sub>20<\/sub>N<sub>2<\/sub>O<sub>2<\/sub> 236.3 99291-25-5<\/p>\n<p><strong>Action and use<\/strong><\/p>\n<p>Cough suppressant.<\/p>\n<h2>DEFINITION<\/h2>\n<p>(2S)-3-(4-Phenylpiperazin-1-yl)propane-1,2-diol.<\/p>\n<h3>Content<\/h3>\n<p>98.5 per cent to 101.0 per cent (dried substance).<\/p>\n<h2>CHARACTERS<\/h2>\n<h3>Appearance<\/h3>\n<p>White or almost white powder.<\/p>\n<h3>Solubility<\/h3>\n<p>Slightly soluble in water, freely soluble in dilute acetic acid and in methanol, slightly soluble in ethanol (96 per cent).<\/p>\n<h2>IDENTIFICATION<\/h2>\n<p>Carry out either tests A, B or tests B, C.<\/p>\n<p>A. Specific optical rotation (2.2.7): -33.5 to -30.0 (dried substance).<\/p>\n<p>Dissolve 1.50 g in a 21 g\/L solution of hydrochloric acid R and dilute to 50.0 mL with the same acid.<\/p>\n<p>B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n<p>Comparison: levodropropizine CRS.<\/p>\n<p>C. Enantiomeric purity (see Tests).<\/p>\n<h2>TESTS<\/h2>\n<h3>pH (2.2.3)<\/h3>\n<p>9.2 to 10.2.<\/p>\n<p>Suspend 2.5 g in carbon dioxide-free water R, heat to dissolve, cool to room temperature and dilute to 100 mL with the same solvent.<\/p>\n<h3>Related substances<\/h3>\n<p>Liquid chromatography (2.2.29).<\/p>\n<p>Test solution: Dissolve 25.0 mg of the substance to be examined in the mobile phase and dilute to 50.0 mL with the mobile phase.<\/p>\n<p>Reference solution (a): Dissolve 25.0 mg of levodropropizine impurity B CRS in methanol R and dilute to 100.0 mL with the same solvent. Dilute 1.0 mL of the solution to 100.0 mL with the mobile phase.<\/p>\n<p>Reference solution (b): Mix 1 mL of the test solution with 1 mL of reference solution (a).<\/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 extra-dense bonded octadecylsilyl silica gel for chromatography R (5 \u03bcm).<\/p>\n<p>Mobile phase: Mix 12 volumes of methanol R and 88 volumes of a 6.81 g\/L solution of potassium dihydrogen phosphate R previously adjusted to pH 3.0 with phosphoric acid R.<\/p>\n<p>Flow rate: 1.5 mL\/min.<\/p>\n<p>Detection: Spectrophotometer at 254 nm.<\/p>\n<p>Injection: 20 \u03bcL.<\/p>\n<p>Run time: Twice the retention time of levodropropizine.<\/p>\n<p>Identification of impurities: Use the chromatogram obtained with reference solution (a) to identify the peak due to impurity B.<\/p>\n<p>Relative retention: With reference to levodropropizine (retention time = about 7 min): impurity B = about 1.2.<\/p>\n<p>System suitability: Reference solution (b):<\/p>\n<p>\u2014 resolution: minimum 2.0 between the peaks due to levodropropizine and impurity B.<\/p>\n<p>Limits:<\/p>\n<p>\u2014 impurity B: 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 unspecified impurities: for each impurity, not more than 0.2 times the area of the peak due to impurity B in the chromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\n<p>\u2014 total: not more than 1.2 times the area of the peak due to impurity B in the chromatogram obtained with reference solution (a) (0.6 per cent);<\/p>\n<p>\u2014 disregard limit: 0.1 times the area of the peak due to impurity B in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n<h3>Impurity C<\/h3>\n<p>Liquid chromatography (2.2.29). Prepare the solutions immediately before use. Use vials sealed with a crimp-top to prevent evaporation of the solvent.<\/p>\n<p>Test solution: Dissolve 50 mg of sodium diethyldithiocarbamate R and 1.0 g of the substance to be examined in methanol R and dilute to 5.0 mL with the same solvent. Heat at 60 \u00b0C for 20 min and then cool to room temperature. Add 5 mL of water R and 0.5 mL of phosphoric acid R. Extract with 5 mL of methylene chloride R.<\/p>\n<p>Reference solution (a): Dissolve 0.100 g of levodropropizine impurity C CRS in methanol R and dilute to 50.0 mL with the same solvent. Dilute 1.0 mL of the solution to 20.0 mL with methanol R. Dilute 1.0 mL of this solution to 100.0 mL with methanol R.<\/p>\n<p>Reference solution (b): Dissolve 50 mg of sodium diethyldithiocarbamate R in reference solution (a) and dilute to 5.0 mL with reference solution (a). Heat at 60 \u00b0C for 20 min and then cool to room temperature. Add 5 mL of water R and 0.5 mL of phosphoric acid R. Extract with 5 mL of methylene chloride R.<\/p>\n<p>Reference solution (c): Dissolve 50 mg of sodium diethyldithiocarbamate R and 1.0 g of the substance to be examined in reference solution (a) and dilute to 5.0 mL with reference solution (a). Heat at 60 \u00b0C for 20 min and then cool to room temperature. Add 5 mL of water R and 0.5 mL of phosphoric acid R. Extract with 5 mL of methylene chloride R.<\/p>\n<p>Blank solution: Dissolve 50 mg of sodium diethyldithiocarbamate R in methanol R and dilute to 5.0 mL with the same solvent. Heat at 60 \u00b0C for 20 min and then cool to room temperature. Add 5 mL of water R and 0.5 mL of phosphoric acid R. Extract with 5 mL of methylene chloride R.<\/p>\n<p>Column:<\/p>\n<p>\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n<p>\u2014 stationary phase: aminopropylsilyl silica gel for chromatography R (5 \u03bcm).<\/p>\n<p>Mobile phase: methanol R, tetrahydrofuran R, heptane R (15:15:70 V\/V\/V).<\/p>\n<p>Flow rate: 1 mL\/min.<\/p>\n<p>Detection: Spectrophotometer at 278 nm.<\/p>\n<p>Injection: 20 \u03bcL of the blank solution, the test solution and reference solutions (b) and (c).<\/p>\n<p>Run time: 3 times the retention time of impurity C.<\/p>\n<p>Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity C.<\/p>\n<p>Retention time Impurity C = about 8 min.<\/p>\n<p>System suitability: Reference solution (b):<\/p>\n<p>\u2014 signal-to-noise ratio: minimum 50 for the peak due to impurity C.<\/p>\n<p>Calculate the content of impurity C in parts per million using the following expression:<\/p>\n<p style=\"text-align: center;\">A \/ (B &#8211; A) x 5<\/p>\n<p>A = area of the peak due to impurity C in the chromatogram obtained with the test solution;<\/p>\n<p>B = area of the peak due to impurity C in the chromatogram obtained with reference solution (c).<\/p>\n<p>Limit:<\/p>\n<p>\u2014 impurity C: maximum 5 ppm.<\/p>\n<h3>Enantiomeric purity<\/h3>\n<p>Liquid chromatography (2.2.29).<\/p>\n<p>Solvent mixture anhydrous ethanol R, hexane R (40:60 V\/V).<\/p>\n<p>Test solution: Dissolve 10.0 mg of the substance to be examined in 10.0 mL of the solvent mixture. Dilute 1.0 mL of the solution to 50.0 mL with the solvent mixture.<\/p>\n<p>Reference solution (a): Dissolve 10 mg of levodropropizine CRS in 10.0 mL of the solvent mixture. Dilute 1.0 mL of the solution to 50.0 mL with the solvent mixture.<\/p>\n<p>Reference solution (b): Dissolve 10.0 mg of levodropropizine impurity A CRS in 10 mL of the solvent mixture. Dilute 1 mL of the solution to 50 mL with the solvent mixture.<\/p>\n<p>Reference solution (c): Dilute 1.0 mL of reference solution (b) to 50.0 mL with the solvent mixture.<\/p>\n<p>Reference solution (d): Dilute 0.5 mL of reference solution (b) to 25 mL with reference solution (a).<\/p>\n<p>Column:<\/p>\n<p>\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n<p>\u2014 stationary phase: cellulose derivative of silica gel for chiral separation R (10 \u03bcm).<\/p>\n<p>Mobile phase diethylamine R, anhydrous ethanol R, hexane R (0.2:5:95 V\/V\/V).<\/p>\n<p>Flow rate: 0.8 mL\/min.<\/p>\n<p>Detection: Spectrophotometer at 254 nm.<\/p>\n<p>Injection: 20 \u03bcL of the test solution and reference solutions (a), (c) and (d).<\/p>\n<p>Identification of impurities: Use the chromatogram obtained with reference solution (c) to identify the peak due to impurity A.<\/p>\n<p>Relative retention: With reference to levodropropizine (retention time = about 28 min): impurity A = about 0.9.<\/p>\n<p>System suitability:<\/p>\n<p>\u2014 retention times: the retention times of the principal peaks in the chromatograms obtained with the test solution and reference solution (a) are similar;<\/p>\n<p>\u2014 resolution: minimum 1.3 between the peaks due to impurity A and levodropropizine in the chromatogram obtained with reference solution (d).<\/p>\n<p>Limit:<\/p>\n<p>\u2014 impurity A: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (2 per cent).<\/p>\n<h3>Loss on drying (2.2.32)<\/h3>\n<p>Maximum 1.0 per cent, determined on 0.500 g by drying in vacuo at 60 \u00b0C at a pressure of 0.15-0.25 kPa for 4 h.<\/p>\n<h3>Sulfated ash (2.4.14)<\/h3>\n<p>Maximum 0.2 per cent, determined on 1.0 g.<\/p>\n<h2>ASSAY<\/h2>\n<p>Dissolve 0.100 g in 50 mL of anhydrous acetic acid R. Carry out a potentiometric titration (2.2.20), using 0.1 M perchloric acid. Read the volume added at the 2 point of inflexion.<\/p>\n<p>1 mL of 0.1 M perchloric acid is equivalent to 11.82 mg of C<sub>13<\/sub>H<sub>20<\/sub>N<sub>2<\/sub>O<sub>2<\/sub>.<\/p>\n<h2>STORAGE<\/h2>\n<p>Protected from light.<\/p>\n<h2>IMPURITIES<\/h2>\n<p>Specified impurities A, B, C.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-17782\" src=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/2-269-300x163.jpg\" alt=\"Levodropropizine\" width=\"300\" height=\"163\" srcset=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/2-269-300x163.jpg 300w, https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/2-269-1024x555.jpg 1024w, https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/2-269-768x416.jpg 768w, https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/2-269.jpg 1200w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/p>\n<p>A. (2R)-3-(4-phenylpiperazin-1-yl)propane-1,2-diol (dextrodropropizine),<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-17783\" src=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/3-253-300x163.jpg\" alt=\"Levodropropizine \" width=\"300\" height=\"163\" srcset=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/3-253-300x163.jpg 300w, https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/3-253-1024x555.jpg 1024w, https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/3-253-768x416.jpg 768w, https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/3-253.jpg 1200w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/p>\n<p>B. 1-phenylpiperazine,<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-17784\" src=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/4-231-300x163.jpg\" alt=\"Levodropropizine \" width=\"300\" height=\"163\" srcset=\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/4-231-300x163.jpg 300w, https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/4-231-1024x555.jpg 1024w, https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/4-231-768x416.jpg 768w, https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/4-231.jpg 1200w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/p>\n<p>C. [(2RS)-oxiran-2-yl]methanol (glycidol).<\/p>\n","protected":false},"excerpt":{"rendered":"<p>(Ph. Eur. monograph 1535) C13H20N2O2 236.3 99291-25-5 Action and use Cough suppressant. DEFINITION (2S)-3-(4-Phenylpiperazin-1-yl)propane-1,2-diol. Content 98.5 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white powder. Solubility Slightly soluble in water, freely soluble in dilute acetic acid and in methanol, slightly soluble in ethanol (96 per cent). IDENTIFICATION Carry out&#8230;<\/p>\n","protected":false},"author":4,"featured_media":17787,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-17767","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\/17767","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=17767"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/17767\/revisions"}],"predecessor-version":[{"id":17793,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/17767\/revisions\/17793"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/17787"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=17767"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=17767"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=17767"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}