{"id":26912,"date":"2025-11-06T14:18:14","date_gmt":"2025-11-06T07:18:14","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=26912"},"modified":"2025-11-06T14:18:14","modified_gmt":"2025-11-06T07:18:14","slug":"papaverine-hydrochloride","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/papaverine-hydrochloride\/","title":{"rendered":"Papaverine Hydrochloride"},"content":{"rendered":"

(Ph. Eur. monograph 0102)<\/p>\n

C_{20<\/sub>H_{22<\/sub>ClNO_{4<\/sub>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 375.9\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 61-25-6<\/p>\n}}}

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

Phosphodiesterase inhibitor; smooth muscle relaxant.<\/p>\n

Preparation<\/strong><\/p>\n

Papaverine Injection<\/p>\n

DEFINITION<\/h2>\n
1-(3,4-Dimethoxybenzyl)-6,7-dimethoxyisoquinoline hydrochloride.<\/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, or white or almost white crystals.<\/p>\n
Solubility<\/h3>\n
Sparingly soluble in water, slightly soluble in ethanol (96 per cent).<\/p>\n
IDENTIFICATION<\/h2>\n
First identification: A, D.<\/p>\n
Second identification: B, C, D.<\/p>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: papaverine hydrochloride CRS.<\/p>\n
B. Thin-layer chromatography (2.2.27).<\/p>\n
Test solution: Dissolve 5 mg of the substance to be examined in methanol R and dilute to 10 mL with the same solvent.<\/p>\n
Reference solution: Dissolve 5 mg of papaverine hydrochloride CRS in methanol R and dilute to 10 mL with the same solvent.<\/p>\n
Plate: TLC silica gel GF254 plate R.<\/p>\n
Mobile phase: diethylamine R, ethyl acetate R, toluene R (10:20:70 V\/V\/V).<\/p>\n
Application: 10 \u03bcL.<\/p>\n
Development: Over 2\/3 of the plate.<\/p>\n
Drying: At 100-105 \u00b0C for 2 h.<\/p>\n
Detection: Examine in ultraviolet light at 254 nm.<\/p>\n
Results: The principal spot in the chromatogram obtained with the test solution is similar in position and size to the principal spot in the chromatogram obtained with the reference solution.<\/p>\n
C. To 10 mL of solution S (see Tests) add 5 mL of ammonia R dropwise and allow to stand for 10 min. The precipitate, washed and dried, melts (2.2.14) at 146 \u00b0C to 149 \u00b0C.<\/p>\n
D. It gives reaction (a) of chlorides (2.3.1).<\/p>\n
TESTS<\/h2>\n
Solution S<\/h3>\n
Dissolve 0.4 g in carbon dioxide-free water R, heating gently if necessary, and dilute to 20 mL with the same solvent.<\/p>\n
Appearance of solution<\/h3>\n
Solution S is clear (2.2.1) and not more intensely coloured than reference solution BY_{6<\/sub> (2.2.2, Method II).<\/p>\n}
pH (2.2.3)<\/h4>\n
3.0 to 4.0 for solution S.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Solvent mixture: acetonitrile R, mobile phase A (20:80 V\/V).<\/p>\n
Test solution: Dissolve 20.0 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n
Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.<\/p>\n
Reference solution (b): Dissolve 12 mg of noscapine CRS in 1.0 mL of the test solution and dilute to 100.0 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.25 m, \u00d8 = 4.0 mm;<\/p>\n
\u2014 stationary phase: base-deactivated octylsilyl silica gel for chromatography R (5 \u03bcm).<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: 3.4 g\/L solution of potassium dihydrogen phosphate R adjusted to pH 3.0 with dilute phosphoric acid R;\\<\/p>\n
\u2014 mobile phase B: acetonitrile R;<\/p>\n
\u2014 mobile phase C: methanol R;<\/p>\n\n\n\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 Mobile phase C<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 5<\/td>\n 85<\/td>\n 5<\/td>\n 10<\/td>\n<\/tr>\n
5 – 12<\/td>\n 85 \u2192 60<\/td>\n 5<\/td>\n 10 \u2192 35<\/td>\n<\/tr>\n
12 – 20<\/td>\n 60<\/td>\n 5<\/td>\n 35<\/td>\n<\/tr>\n
20 – 24<\/td>\n 60 \u2192 40<\/td>\n 5 \u2192 20<\/td>\n 35 \u2192 40<\/td>\n<\/tr>\n
24 – 27<\/td>\n 40<\/td>\n 20<\/td>\n 40<\/td>\n<\/tr>\n
27 – 32<\/td>\n 40 \u2192 85<\/td>\n 20 \u2192 5<\/td>\n 40 \u2192 10<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1 mL\/min.<\/p>\n
Detection: Spectrophotometer at 238 nm.<\/p>\n
Injection: 10 \u03bcL.<\/p>\n
Relative retention: With reference to papaverine (retention time = about 24 min): impurity E = about 0.7; impurity C = about 0.75; impurity B = about 0.8; impurity A = about 0.9; impurity F = about 1.1; impurity D = about 1.2.<\/p>\n
System suitability: Reference solution (b):<\/p>\n
\u2014 resolution: minimum 1.5 between the peaks due to impurity A and papaverine.<\/p>\n
Limits:<\/p>\n
\u2014 correction factors: for the calculation of contents, multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 6.2; impurity C = 2.7; impurity D = 0.5;<\/p>\n
\u2014 any impurity: not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 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: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n
Loss on drying (2.2.32)<\/h4>\n
Maximum 0.5 per cent, determined on 1.000 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 the residue from the test for loss on drying.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.300 g in a mixture of 5.0 mL of 0.01 M hydrochloric acid and 50 mL of alcohol R. Carry out a potentiometric titration (2.2.20), using 0.1 M sodium hydroxide. Read the volume added between the 2 points of inflexion.<\/p>\n
1 mL of 0.1 M sodium hydroxide is equivalent to 37.59 mg of C_{20<\/sub>H_{22<\/sub>ClNO_{4<\/sub>.<\/p>\n}}}
IMPURITIES<\/h2>\n
$\"Papaverine$ <\/p>\n
A. (3S)-6,7-dimethoxy-3-[(5R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinolin-5-yl]isobenzofuran-1(3H)-one (noscapine),<\/p>\n
$\"Papaverine$ <\/p>\n
B. (RS)-(3,4-dimethoxyphenyl)(6,7-dimethoxyisoquinolin-1-yl)methanol (papaverinol),<\/p>\n
$\"Papaverine$ <\/p>\n
C. 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline (dihydropapaverine),<\/p>\n
$\"Papaverine$ <\/p>\n
D. (3,4-dimethoxyphenyl)(6,7-dimethoxyisoquinolin-1-yl)methanone (papaveraldine),<\/p>\n
$\"Papaverine$ <\/p>\n
E. (1RS)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (tetrahydropapaverine),<\/p>\n
$\"Papaverine$ <\/p>\n
F. 2-(3,4-dimethoxyphenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 0102) C20H22ClNO4\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 375.9\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 61-25-6 Action and use Phosphodiesterase inhibitor; smooth muscle relaxant. Preparation Papaverine Injection DEFINITION 1-(3,4-Dimethoxybenzyl)-6,7-dimethoxyisoquinoline hydrochloride. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder, or white or almost white crystals. Solubility…<\/p>\n","protected":false},"author":2,"featured_media":26935,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26912","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\/26912","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=26912"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26912\/revisions"}],"predecessor-version":[{"id":26937,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26912\/revisions\/26937"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26935"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26912"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26912"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26912"}],"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	Mobile phase C<\/strong> \n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 5<\/td>\n	85<\/td>\n	5<\/td>\n	10<\/td>\n<\/tr>\n
5 – 12<\/td>\n	85 \u2192 60<\/td>\n	5<\/td>\n	10 \u2192 35<\/td>\n<\/tr>\n
12 – 20<\/td>\n	60<\/td>\n	5<\/td>\n	35<\/td>\n<\/tr>\n
20 – 24<\/td>\n	60 \u2192 40<\/td>\n	5 \u2192 20<\/td>\n	35 \u2192 40<\/td>\n<\/tr>\n
24 – 27<\/td>\n	40<\/td>\n	20<\/td>\n	40<\/td>\n<\/tr>\n
27 – 32<\/td>\n	40 \u2192 85<\/td>\n	20 \u2192 5<\/td>\n	40 \u2192 10<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 1 mL\/min.<\/p>\n Detection: Spectrophotometer at 238 nm.<\/p>\n Injection: 10 \u03bcL.<\/p>\n Relative retention: With reference to papaverine (retention time = about 24 min): impurity E = about 0.7; impurity C = about 0.75; impurity B = about 0.8; impurity A = about 0.9; impurity F = about 1.1; impurity D = about 1.2.<\/p>\n System suitability: Reference solution (b):<\/p>\n \u2014 resolution: minimum 1.5 between the peaks due to impurity A and papaverine.<\/p>\n Limits:<\/p>\n \u2014 correction factors: for the calculation of contents, multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 6.2; impurity C = 2.7; impurity D = 0.5;<\/p>\n \u2014 any impurity: not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 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: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n Loss on drying (2.2.32)<\/h4>\n Maximum 0.5 per cent, determined on 1.000 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 the residue from the test for loss on drying.<\/p>\n ASSAY<\/h2>\n Dissolve 0.300 g in a mixture of 5.0 mL of 0.01 M hydrochloric acid and 50 mL of alcohol R. Carry out a potentiometric titration (2.2.20), using 0.1 M sodium hydroxide. Read the volume added between the 2 points of inflexion.<\/p>\n 1 mL of 0.1 M sodium hydroxide is equivalent to 37.59 mg of C_{20<\/sub>H_{22<\/sub>ClNO_{4<\/sub>.<\/p>\n}}} IMPURITIES<\/h2>\n $\"Papaverine$ <\/p>\n A. (3S)-6,7-dimethoxy-3-[(5R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinolin-5-yl]isobenzofuran-1(3H)-one (noscapine),<\/p>\n $\"Papaverine$ <\/p>\n B. (RS)-(3,4-dimethoxyphenyl)(6,7-dimethoxyisoquinolin-1-yl)methanol (papaverinol),<\/p>\n $\"Papaverine$ <\/p>\n C. 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline (dihydropapaverine),<\/p>\n $\"Papaverine$ <\/p>\n D. (3,4-dimethoxyphenyl)(6,7-dimethoxyisoquinolin-1-yl)methanone (papaveraldine),<\/p>\n $\"Papaverine$ <\/p>\n E. (1RS)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (tetrahydropapaverine),<\/p>\n $\"Papaverine$ <\/p>\n F. 2-(3,4-dimethoxyphenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide.<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 0102) C20H22ClNO4\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 375.9\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 61-25-6 Action and use Phosphodiesterase inhibitor; smooth muscle relaxant. Preparation Papaverine Injection DEFINITION 1-(3,4-Dimethoxybenzyl)-6,7-dimethoxyisoquinoline hydrochloride. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder, or white or almost white crystals. Solubility…<\/p>\n","protected":false},"author":2,"featured_media":26935,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26912","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\/26912","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=26912"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26912\/revisions"}],"predecessor-version":[{"id":26937,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26912\/revisions\/26937"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26935"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26912"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26912"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26912"}],"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, or white or almost white crystals.<\/p>\n

Solubility<\/h3>\nSparingly soluble in water, slightly soluble in ethanol (96 per cent).<\/p>\n

TESTS<\/h2>\n

Solution S<\/h3>\nDissolve 0.4 g in carbon dioxide-free water R, heating gently if necessary, and dilute to 20 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\nSolution S is clear (2.2.1) and not more intensely coloured than reference solution BY6<\/sub> (2.2.2, Method II).<\/p>\n

pH (2.2.3)<\/h4>\n3.0 to 4.0 for solution S.<\/p>\n

Loss on drying (2.2.32)<\/h4>\nMaximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.1 per cent, determined on the residue from the test for loss on drying.<\/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, or white or almost white crystals.<\/p>\n

Solubility<\/h3>\n
Sparingly soluble in water, slightly soluble in ethanol (96 per cent).<\/p>\n

Solution S<\/h3>\n
Dissolve 0.4 g in carbon dioxide-free water R, heating gently if necessary, and dilute to 20 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n
Solution S is clear (2.2.1) and not more intensely coloured than reference solution BY_{6<\/sub> (2.2.2, Method II).<\/p>\n}

pH (2.2.3)<\/h4>\n
3.0 to 4.0 for solution S.<\/p>\n

Loss on drying (2.2.32)<\/h4>\n
Maximum 0.5 per cent, determined on 1.000 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 the residue from the test for loss on drying.<\/p>\n