{"id":16831,"date":"2025-10-21T11:44:19","date_gmt":"2025-10-21T04:44:19","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=16831"},"modified":"2025-10-21T11:44:19","modified_gmt":"2025-10-21T04:44:19","slug":"levodopa","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/levodopa\/","title":{"rendered":"Levodopa"},"content":{"rendered":"

(Ph. Eur. monograph 0038)<\/p>\n

C_{9<\/sub>H_{11<\/sub>NO_{4<\/sub>\u00a0 \u00a0 \u00a0 197.2\u00a0 \u00a0 \u00a0 59-92-7<\/p>\n}}}

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

Dopamine precursor; treatment of Parkinson\u2019s disease.<\/p>\n

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

Co-beneldopa Capsules<\/p>\n

Co-beneldopa Dispersible Tablets<\/p>\n

Co-beneldopa Prolonged-release Capsules<\/p>\n

Co-careldopa Tablets<\/p>\n

When L-dopa is prescribed or demanded, Levodopa shall be dispensed or supplied.<\/p>\n

DEFINITION<\/h2>\n
(2S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid.<\/p>\n
Content<\/h3>\n
99.0 per cent to 101.0 per cent (dried substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white, crystalline powder.<\/p>\n
Solubility<\/h3>\n
Slightly soluble in water, practically insoluble in ethanol (96 per cent). It is freely soluble in 1 M hydrochloric acid and sparingly soluble in 0.1 M hydrochloric acid.<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: levodopa CRS.<\/p>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
The solution is not more intensely coloured than reference solution BY6 (2.2.2, Method II).<\/p>\n
Dissolve 1.0 g in a 103 g\/L solution of hydrochloric acid R and dilute to 25 mL with the same solution.<\/p>\n
pH (2.2.3)<\/h4>\n
4.5 to 7.0.<\/p>\n
Shake 0.10 g with 10 mL of carbon dioxide-free water R for 15 min.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Use freshly prepared solutions.<\/p>\n
Solution A: 10.3 g\/L solution of hydrochloric acid R.<\/p>\n
Test solution: Dissolve 0.100 g of the substance to be examined in solution A and dilute to 25 mL with solution A.<\/p>\n
Reference solution (a): Dilute 1.0 mL of the test solution to 50.0 mL with solution A. Dilute 5.0 mL of this solution to 100.0 mL with solution A.<\/p>\n
Reference solution (b): Dissolve 8 mg of tyrosine R (impurity B) and 4 mg of 3-methoxy-L-tyrosine R (L- isomer of impurity C) in 2 mL of the test solution and dilute to 50 mL with solution A. Dilute 5 mL of this solution to 100 mL with solution A.<\/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 \u03bcm) with a pore size of 8 nm.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: 0.1 M phosphate buffer solution pH 3.0 R;<\/p>\n
\u2014 mobile phase B: methanol R, 0.1 M phosphate buffer solution pH 3.0 R (18:85 V\/V);<\/p>\n\n\n\n\n\n\n
Time<\/strong>
\n(min)<\/strong><\/td>\n Mobile phase A<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n Mobile phase B<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 18<\/td>\n 90<\/td>\n 10<\/td>\n<\/tr>\n
18 – 22<\/td>\n 90 \u2192 0<\/td>\n 10 \u2192 100<\/td>\n<\/tr>\n
22 – 35<\/td>\n 0<\/td>\n 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1 mL\/min.<\/p>\n
Detection: Spectrophotometer at 280 nm.<\/p>\n
Injection: 20 \u03bcL.<\/p>\n
Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peaks due to impurities B and C.<\/p>\n
Relative retention: With reference to levodopa (retention time = about 6 min): impurity A = about 0.7; impurity B = about 2; impurity C = about 3.5.<\/p>\n
System suitability: Reference solution (b):<\/p>\n
\u2014 resolution: minimum 10 between the peaks due to levodopa and impurity B.<\/p>\n
Limits:<\/p>\n
\u2014 correction factor: for the calculation of content, multiply the peak area of impurity B by 2.2;<\/p>\n
\u2014 impurity B: 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 impurity C: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent);<\/p>\n
\u2014 impurity A: not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 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 10 times the area of the principal peak in the chromatogram obtained with reference solution (a) (1.0 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
Enantiomeric purity<\/h3>\n
Liquid chromatography (2.2.29). Use freshly prepared solutions.<\/p>\n
Test solution: Dissolve 25 mg of the substance to be examined in the mobile phase and dilute to 25 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 10 mg of D-dopa R (impurity D) in 10 mL of the test solution. Dilute 1 mL of this solution to 100 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 \u03bcm).<\/p>\n
Mobile phase: Dissolve separately 200 mg of copper acetate R and 387 mg of N,N-dimethyl-L- phenylalanine R in 250 mL of water R; mix the 2 solutions and adjust immediately to pH 4.0 with acetic acid R; add 50 mL of methanol R and dilute to 1000 mL with water R; mix and filter.<\/p>\n
Flow rate: 1 mL\/min.<\/p>\n
Detection: Spectrophotometer at 280 nm.<\/p>\n
Injection: 20 \u03bcL.<\/p>\n
Run time: Twice the retention time of levodopa.<\/p>\n
Relative retention: With reference to levodopa (retention time = about 7 min): impurity D = about 0.4.<\/p>\n
System suitability: Reference solution (b):<\/p>\n
\u2014 resolution: minimum 5 between the peaks due to impurity D and levodopa.<\/p>\n
Limit:<\/p>\n
\u2014 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
Loss on drying (2.2.32)<\/h4>\n
Maximum 1.0 per cent, determined on 0.500 g by drying in an oven at 105 \u00b0C.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.150 g, heating if necessary, in 5 mL of anhydrous formic acid R. Add 50 mL of anhydrous 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 19.72 mg of C_{9<\/sub>H_{11<\/sub>NO_{4<\/sub>.<\/p>\n}}}
STORAGE<\/h2>\n
Protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities A, B, C, D.<\/p>\n
$\"Levodopa\"$ <\/p>\n
A. (2S)-2-amino-3-(2,4,5-trihydroxyphenyl)propanoic acid,<\/p>\n
$\"Levodopa\"$ <\/p>\n
B. (2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid (tyrosine),<\/p>\n
$\"Levodopa\"$ <\/p>\n
C. (2RS)-2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoic acid (3-methoxy-DL-tyrosine),<\/p>\n
$\"Levodopa\"$ <\/p>\n
D. (2R)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid (D-dopa).<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 0038) C9H11NO4\u00a0 \u00a0 \u00a0 197.2\u00a0 \u00a0 \u00a0 59-92-7 Action and use Dopamine precursor; treatment of Parkinson\u2019s disease. Preparations Co-beneldopa Capsules Co-beneldopa Dispersible Tablets Co-beneldopa Prolonged-release Capsules Co-careldopa Tablets When L-dopa is prescribed or demanded, Levodopa shall be dispensed or supplied. DEFINITION (2S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid. Content 99.0 per cent to 101.0 per cent (dried…<\/p>\n","protected":false},"author":2,"featured_media":16848,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-16831","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\/16831","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=16831"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/16831\/revisions"}],"predecessor-version":[{"id":16856,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/16831\/revisions\/16856"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/16848"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=16831"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=16831"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=16831"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time<\/strong> \n(min)<\/strong><\/td>\n	Mobile phase A<\/strong> \n(per cent V\/V)<\/strong><\/td>\n	Mobile phase B<\/strong> \n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 18<\/td>\n	90<\/td>\n	10<\/td>\n<\/tr>\n
18 – 22<\/td>\n	90 \u2192 0<\/td>\n	10 \u2192 100<\/td>\n<\/tr>\n
22 – 35<\/td>\n	0<\/td>\n	100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 1 mL\/min.<\/p>\n Detection: Spectrophotometer at 280 nm.<\/p>\n Injection: 20 \u03bcL.<\/p>\n Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peaks due to impurities B and C.<\/p>\n Relative retention: With reference to levodopa (retention time = about 6 min): impurity A = about 0.7; impurity B = about 2; impurity C = about 3.5.<\/p>\n System suitability: Reference solution (b):<\/p>\n \u2014 resolution: minimum 10 between the peaks due to levodopa and impurity B.<\/p>\n Limits:<\/p>\n \u2014 correction factor: for the calculation of content, multiply the peak area of impurity B by 2.2;<\/p>\n \u2014 impurity B: 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 impurity C: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent);<\/p>\n \u2014 impurity A: not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 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 10 times the area of the principal peak in the chromatogram obtained with reference solution (a) (1.0 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 Enantiomeric purity<\/h3>\n Liquid chromatography (2.2.29). Use freshly prepared solutions.<\/p>\n Test solution: Dissolve 25 mg of the substance to be examined in the mobile phase and dilute to 25 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 10 mg of D-dopa R (impurity D) in 10 mL of the test solution. Dilute 1 mL of this solution to 100 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 \u03bcm).<\/p>\n Mobile phase: Dissolve separately 200 mg of copper acetate R and 387 mg of N,N-dimethyl-L- phenylalanine R in 250 mL of water R; mix the 2 solutions and adjust immediately to pH 4.0 with acetic acid R; add 50 mL of methanol R and dilute to 1000 mL with water R; mix and filter.<\/p>\n Flow rate: 1 mL\/min.<\/p>\n Detection: Spectrophotometer at 280 nm.<\/p>\n Injection: 20 \u03bcL.<\/p>\n Run time: Twice the retention time of levodopa.<\/p>\n Relative retention: With reference to levodopa (retention time = about 7 min): impurity D = about 0.4.<\/p>\n System suitability: Reference solution (b):<\/p>\n \u2014 resolution: minimum 5 between the peaks due to impurity D and levodopa.<\/p>\n Limit:<\/p>\n \u2014 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 Loss on drying (2.2.32)<\/h4>\n Maximum 1.0 per cent, determined on 0.500 g by drying in an oven at 105 \u00b0C.<\/p>\n Sulfated ash (2.4.14)<\/h4>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n ASSAY<\/h2>\n Dissolve 0.150 g, heating if necessary, in 5 mL of anhydrous formic acid R. Add 50 mL of anhydrous 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 19.72 mg of C_{9<\/sub>H_{11<\/sub>NO_{4<\/sub>.<\/p>\n}}} STORAGE<\/h2>\n Protected from light.<\/p>\n IMPURITIES<\/h2>\n Specified impurities A, B, C, D.<\/p>\n $\"Levodopa\"$ <\/p>\n A. (2S)-2-amino-3-(2,4,5-trihydroxyphenyl)propanoic acid,<\/p>\n $\"Levodopa\"$ <\/p>\n B. (2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid (tyrosine),<\/p>\n $\"Levodopa\"$ <\/p>\n C. (2RS)-2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoic acid (3-methoxy-DL-tyrosine),<\/p>\n $\"Levodopa\"$ <\/p>\n D. (2R)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid (D-dopa).<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 0038) C9H11NO4\u00a0 \u00a0 \u00a0 197.2\u00a0 \u00a0 \u00a0 59-92-7 Action and use Dopamine precursor; treatment of Parkinson\u2019s disease. Preparations Co-beneldopa Capsules Co-beneldopa Dispersible Tablets Co-beneldopa Prolonged-release Capsules Co-careldopa Tablets When L-dopa is prescribed or demanded, Levodopa shall be dispensed or supplied. DEFINITION (2S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid. Content 99.0 per cent to 101.0 per cent (dried…<\/p>\n","protected":false},"author":2,"featured_media":16848,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-16831","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\/16831","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=16831"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/16831\/revisions"}],"predecessor-version":[{"id":16856,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/16831\/revisions\/16856"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/16848"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=16831"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=16831"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=16831"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or almost white, crystalline powder.<\/p>\n

Solubility<\/h3>\nSlightly soluble in water, practically insoluble in ethanol (96 per cent). It is freely soluble in 1 M hydrochloric acid and sparingly soluble in 0.1 M hydrochloric acid.<\/p>\n

IDENTIFICATION<\/h2>\nInfrared absorption spectrophotometry (2.2.24).<\/p>\nComparison: levodopa CRS.<\/p>\n

TESTS<\/h2>\n

Appearance of solution<\/h3>\nThe solution is not more intensely coloured than reference solution BY6 (2.2.2, Method II).<\/p>\nDissolve 1.0 g in a 103 g\/L solution of hydrochloric acid R and dilute to 25 mL with the same solution.<\/p>\n

pH (2.2.3)<\/h4>\n4.5 to 7.0.<\/p>\nShake 0.10 g with 10 mL of carbon dioxide-free water R for 15 min.<\/p>\n

Loss on drying (2.2.32)<\/h4>\nMaximum 1.0 per cent, determined on 0.500 g by drying in an oven at 105 \u00b0C.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.1 per cent, determined on 1.0 g.<\/p>\n

STORAGE<\/h2>\nProtected from light.<\/p>\n

Content<\/h3>\n
99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

Appearance<\/h3>\n
White or almost white, crystalline powder.<\/p>\n

Solubility<\/h3>\n
Slightly soluble in water, practically insoluble in ethanol (96 per cent). It is freely soluble in 1 M hydrochloric acid and sparingly soluble in 0.1 M hydrochloric acid.<\/p>\n

IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: levodopa CRS.<\/p>\n

Appearance of solution<\/h3>\n
The solution is not more intensely coloured than reference solution BY6 (2.2.2, Method II).<\/p>\n
Dissolve 1.0 g in a 103 g\/L solution of hydrochloric acid R and dilute to 25 mL with the same solution.<\/p>\n

pH (2.2.3)<\/h4>\n
4.5 to 7.0.<\/p>\n
Shake 0.10 g with 10 mL of carbon dioxide-free water R for 15 min.<\/p>\n

Loss on drying (2.2.32)<\/h4>\n
Maximum 1.0 per cent, determined on 0.500 g by drying in an oven at 105 \u00b0C.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

STORAGE<\/h2>\n
Protected from light.<\/p>\n