General Notices\u00a0<\/strong><\/p>\n (Ph. Eur. monograph 0045)<\/p>\n C10<\/sub>H13<\/sub>NO4<\/sub>,1\u00bdH2O \u2003 238.2\u2003 41372-08-1<\/p>\n Action and use\u00a0<\/strong><\/p>\n Alpha2<\/sub>-adrenoceptor agonist; treatment of hypertension.<\/p>\n Preparation<\/p>\n Methyldopa Tablets<\/p>\n Ph Eur<\/p>\n (2S)-2-Amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid sesquihydrate (L-methyldopa sesquihydrate).<\/p>\n Content\u00a0<\/strong><\/p>\n 99.0 per cent to 101.0 per cent (anhydrous substance).<\/p>\n Appearance<\/strong><\/p>\n White or yellowish-white, crystalline powder or colourless or almost colourless crystals.<\/p>\n Solubility\u00a0<\/strong><\/p>\n Slightly soluble in water, very slightly soluble in ethanol (96 per cent). It is freely soluble in dilute mineral acids.<\/p>\n Carry out either tests A, B or tests A, C.<\/p>\n A.\u2003Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison methyldopa CRS.<\/p>\n B.\u2003Enantiomeric purity (see Tests).<\/p>\n C.\u2003Specific optical rotation (2.2.7): -28.0 to -25.0.<\/p>\n Dissolve a quantity equivalent to 2.20 g of the anhydrous substance in aluminium chloride solution R and dilute to 50.0 mL with the same solution.<\/p>\n Appearance of solution<\/p>\n Dissolve 1.0 g in 1 M hydrochloric acid and dilute to 25 mL with the same solvent. The solution is not more intensely coloured than reference solution BY6 or B6 (2.2.2, Method II).<\/p>\n Dissolve 1.0 g with heating in 100 mL of carbon dioxide-free water R. Add 0.1 mL of methyl red solution R. Not more than 0.5 mL of 0.1 M sodium hydroxide is required to produce the pure yellow colour of the indicator.<\/p>\n Test solution Dissolve 40.0 mg in 0.1 M hydrochloric acid and dilute to 100.0 mL with the same acid. Dilute 10.0 mL of the solution to 100.0 mL with 0.1 M hydrochloric acid.<\/p>\n Spectral range 230-350 nm.<\/p>\n Absorption maximum At 280 nm.<\/p>\n Specific absorbance at the absorption maximum 122 to 137 (anhydrous substance).<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution Dissolve 25 mg of the substance to be examined in the mobile phase and dilute to 25.0 mL with the mobile phase.<\/p>\n Reference solution (a) Dilute 5.0 mL of the test solution to 20.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 50.0 mL with the mobile phase.<\/p>\n Reference solution (b) Dissolve 2 mg of racemic methyldopa CRS in the mobile phase and dilute to 10.0 mL with the mobile phase.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.15 m, \u00d8 = 3.9 mm;<\/p>\n \u2014 stationary phase: spherical end-capped octadecylsilyl silica gel for chromatography R (5 \u00b5m).<\/p>\n Mobile phase Dissolve separately 0.200 g of copper acetate R and 0.387 g of N,N-dimethyl-L phenylalanine R in water R; mix the 2 solutions and adjust immediately to pH 4.3 with acetic acid R; add 50 mL of methanol R and dilute to 1000 mL with water R; mix and filter.<\/p>\n Equilibrate the column with the mobile phase for about 2 h.<\/p>\n If necessary, decrease the concentration of methanol R so the peak corresponding to D-methyldopa is clearly separated from the negative system peak that appears at about 6 min.<\/p>\n Flow rate 1 mL\/min.<\/p>\n Detection Spectrophotometer at 280 nm.<\/p>\n Injection 20 \u00b5L.<\/p>\n Run time Twice the retention time of L-methyldopa.<\/p>\n Relative retention With reference to L-methyldopa (retention time = about 14 min): D methyldopa = about 0.7.<\/p>\n System suitability Reference solution (b):<\/p>\n \u2014 resolution: minimum 5.0 between the peaks due to D-methyldopa and L-methyldopa. Limit:<\/p>\n \u2014 D-methyldopa (impurity D): not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent).<\/p>\n Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n Test solution Dissolve 0.100 g of the substance to be examined in 0.1 M hydrochloric acid and dilute to 25.0 mL with the same acid.<\/p>\n Reference solution (a) Dilute 1.0 mL of the test solution to 50.0 mL with 0.1 M hydrochloric acid. Dilute 5.0 mL of this solution to 100.0 mL with 0.1 M hydrochloric acid.<\/p>\n Reference solution (b) Dissolve the contents of a vial of methyldopa for system suitability CRS (containing impurities A, B and C) in 1.0 mL of 0.1 M hydrochloric acid.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: spherical di-isobutyloctadecylsilyl silica gel for chromatography R (5 \u00b5m) with a pore size of 8 nm.<\/p>\n Mobile phase methanol R, 0.1 M phosphate buffer solution pH 3.0 R (15:85 V\/V). Flow rate 1 mL\/min.<\/p>\n Detection Spectrophotometer at 280 nm.<\/p>\n Injection 20 \u00b5L.<\/p>\n Run time 6 times the retention time of methyldopa.<\/p>\n Identification of impurities Use the chromatogram supplied with methyldopa for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A, B and C.<\/p>\n Relative retention With reference to methyldopa (retention time = about 5 min): impurity A = about 1.9; impurity B = about 4.3; impurity C = about 4.9.<\/p>\n System suitability Reference solution (b):<\/p>\n \u2014 resolution: minimum 2.0 between the peaks due to impurities B and C.<\/p>\n Limits:<\/p>\n \u2014 correction factors: for the calculation of content, multiply the peak areas of the following impurities by the corresponding correction factor: impurity B = 2.6; impurity C = 1.3;<\/p>\n \u2014 impurities A, B, C: for each impurity, not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.15 per cent);<\/p>\n \u2014 unspecified impurities: for each impurity, not more than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent);<\/p>\n \u2014 total: not more than 5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent);<\/p>\n \u2014 disregard limit: 0.3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.03 per cent).<\/p>\n 10.0 per cent to 13.0 per cent, determined on 0.20 g.<\/p>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n Dissolve 0.180 g, heating if necessary, in 50 mL of glacial acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).<\/p>\n 1 mL of 0.1 M perchloric acid is equivalent to 21.12 mg of C10H13NO4.<\/p>\n Protected from light.<\/p>\n Specified impurities A, B, C, D.<\/p>\n \u200b<\/span><\/p>\n \u200b<\/span><\/p>\n Edition: BP 2025 (Ph. Eur. 11.6 update) Methyldopa \u200b General Notices\u00a0 (Ph. Eur. monograph 0045) C10H13NO4,1\u00bdH2O \u2003 238.2\u2003 41372-08-1 Action and use\u00a0 Alpha2-adrenoceptor agonist; treatment of hypertension. Preparation Methyldopa Tablets Ph Eur DEFINITION (2S)-2-Amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid sesquihydrate (L-methyldopa sesquihydrate). Content\u00a0 99.0 per cent to 101.0 per cent (anhydrous substance). CHARACTERS Appearance White or yellowish-white, crystalline powder…<\/p>\n","protected":false},"author":5,"featured_media":28127,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-28126","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\/28126","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=28126"}],"version-history":[{"count":1,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28126\/revisions"}],"predecessor-version":[{"id":28146,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28126\/revisions\/28146"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/28127"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=28126"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=28126"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=28126"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n
CHARACTERS<\/h2>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
Acidity<\/h3>\n
Absorbance (2.2.25)<\/h3>\n
Enantiomeric purity<\/h3>\n
Related substances<\/h3>\n
Water (2.5.12)<\/h3>\n
Sulfated ash (2.4.14)<\/h3>\n
ASSAY<\/h2>\n
STORAGE<\/h2>\n
IMPURITIES<\/h2>\n
![\"A.\u2003(2S)-2-amino-3-(4-hydroxy-3-methoxyphenyl)-2-methylpropanoic](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/11\/Methyldopa-2.jpg\")
![\"B.\u2003(2S)-2-amino-3-(4-methoxyphenyl)-2-methylpropanoic](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/11\/Methyldopa-3.jpg\")
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![\"D.\u2003(2R)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/11\/Methyldopa-5.jpg\")