{"id":25547,"date":"2025-11-04T15:37:47","date_gmt":"2025-11-04T08:37:47","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=25547"},"modified":"2025-11-04T16:21:09","modified_gmt":"2025-11-04T09:21:09","slug":"nadolol","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/nadolol\/","title":{"rendered":"Nadolol"},"content":{"rendered":"

Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n

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

Beta-adrenoceptor antagonist.<\/p>\n

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

Nadolol Oral Suspension Ph Eur<\/p>\n

DEFINITION<\/h2>\n
cis-5-[(2RS)-3-[(1,1-Dimethylethyl)amino]-2-hydroxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol.<\/p>\n
It consists of 2 pairs of enantiomers that are present as 2 racemic compounds: racemate A and racemate B.<\/p>\n
Content<\/strong><\/p>\n
98.5 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, freely soluble in ethanol (96 per cent), practically insoluble in acetone.<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison\u00a0 nadolol CRS.<\/p>\n
TESTS<\/h2>\n
Racemate content<\/h3>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Prepare a mull in liquid paraffin R of the substance to be examined (dried substance), adjusting the thickness of the mull to give an absorbance reading of 0.6 \u00b1 0.1 at 1587 cm-1. Record the spectrum from 1667 to 1111 cm-1, using liquid paraffin R as reference. Measure the absorbance A , corresponding to racemate A, at the maximum at 1266 cm-1 and the absorbance A , corresponding to racemate B, at the maximum at 1250 cm-1. The ratio A \/A is 0.72 to 1.08 (corresponding to racemate A content of between 40 per cent and 60 per cent).<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Prepare the solutions immediately before use. Solvent mixture\u00a0 acetonitrile R1, water R (20:80 V\/V).<\/p>\n
Test solution<\/em>\u00a0 Dissolve 0.100 g of the substance to be examined in 4.0 mL of the solvent mixture and dilute to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (a)<\/em>\u00a0 Dilute 1.0 mL of the test solution to 50.0 mL with the solvent mixture. Dilute 5.0 mL of this solution to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (b)<\/em>\u00a0 Dissolve the contents of a vial of nadolol impurity mixture CRS (impurities A and D) in 1.0 mL of reference solution (a).<\/p>\n
Column:<\/em><\/p>\n
\u2014 size: l<\/em> = 0.25 m, \u00d8 = 4.0 mm;<\/p>\n
\u2014 stationary phase:<\/em> end-capped octadecylsilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n
\u2014 temperature:<\/em> 40 \u00b0C.<\/p>\n
Mobile phase:<\/em><\/p>\n
\u2014 mobile phase A:<\/em> 5.6 g\/L solution of sodium octanesulfonate R adjusted to pH 3.5 with a 300 g\/L solution of phosphoric acid R;<\/p>\n
\u2014 mobile phase B:<\/em> acetonitrile R1;<\/p>\n\n\n\n\n\n\n\n
Time (min)<\/strong><\/td>\n Mobile phase A (per cent V\/V)<\/strong><\/td>\n Mobile phase B (per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 7<\/td>\n 77<\/td>\n 23<\/td>\n<\/tr>\n
7 – 30<\/td>\n 77 \u2192 65<\/td>\n 23 \u2192 35<\/td>\n<\/tr>\n
30 – 35<\/td>\n 65 \u2192 55<\/td>\n 35 \u2192 45<\/td>\n<\/tr>\n
35 – 55<\/td>\n 55<\/td>\n 45<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate<\/em>\u00a0 1 mL\/min.<\/p>\n
Detection<\/em>\u00a0 Spectrophotometer at 206 nm.<\/p>\n
Injection<\/em>\u00a0 20 \u00b5L.<\/p>\n
Identification of impurities\u00a0<\/em> Use the chromatogram supplied with nadolol impurity mixture CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A and D.<\/p>\n
Relative retention<\/em>\u00a0 With reference to nadolol (retention time = about 15 min): impurity A = about 0.2; impurity C (doublet) = about 0.47 and 0.53; impurity D = about 1.5.<\/p>\n
System suitability\u00a0<\/em> Reference solution (b):<\/p>\n
\u2014 resolution:<\/em> minimum 8.0 between the peaks due to nadolol and impurity D.<\/p>\n
Limits:<\/em><\/p>\n
\u2014 correction factor:<\/em> for the calculation of content, multiply the sum of the 2 peak areas of impurity C by 0.7;<\/p>\n
\u2014 impurities A, C, D:<\/em> for each impurity, 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 unspecified impurities:<\/em> for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\n
\u2014 total:<\/em> 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:<\/em> 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)<\/strong><\/p>\n
Maximum 2.0 per cent, determined on 1.000 g by drying in vacuo at 60 \u00b0C for 3 h.<\/p>\n
Sulfated ash (2.4.14)<\/strong><\/p>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.250 g in 100 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).<\/p>\n
l mL of 0.1 M perchloric acid is equivalent to 30.94 mg of C_{17<\/sub>H_{27<\/sub>NO_{4<\/sub>.<\/p>\n}}}
IMPURITIES<\/h2>\n
Specified impurities\u00a0 A, C, D.<\/em><\/p>\n
Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10.<\/em><\/p>\n
Control of impurities in substances for pharmaceutical use)\u00a0 B, E, F, G.<\/em><\/p>\n
$\"Nadolol\"$ <\/p>\n
A. cis-5-[(2RS)-2,3-dihydroxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol (tetraol),<\/p>\n
$\"Nadolol\"$ <\/p>\n
B. cis-5-[(2RS)-2-hydroxy-3-methoxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol,<\/p>\n
$\"Nadolol\"$ <\/p>\n
C. 5,5\u2032-[(2rs)-2-hydroxypropane-1,3-diylbis(oxy)]bis(cis-1,2,3,4-tetrahydronaphthalene-2,3-diol) (3 diastereoisomers),<\/p>\n
$\"Nadolol\"$ <\/p>\n
D. 5,5\u2032-[[(1,1-dimethylethyl)imino]bis[(2-hydroxypropane-1,3-diyl)oxy]]bis(cis-1,2,3,4- tetrahydronaphthalene-2,3-diol) (10 stereoisomers),<\/p>\n
$\"Nadolol\"$ <\/p>\n
E. cis-5-[(2RS)-3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-8-iodo-1,2,3,4-tetrahydronaphthalene-2,3-\u00a0 diol,<\/p>\n
$\"Nadolol\"$ <\/p>\n
F. (2RS)-1-[(1,1-dimethylethyl)amino]-3-(naphthalen-1-yloxy)propan-2-ol,<\/p>\n
$\"Nadolol\"$ <\/p>\n
G. (2RS)-1-[(1,1-dimethylethyl)amino]-3-[(5,6,7,8-tetrahydronaphthalen-1-yl)oxy]propan-2-ol.<\/p>\n
\n
Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":"
Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Beta-adrenoceptor antagonist. Preparation Nadolol Oral Suspension Ph Eur DEFINITION cis-5-[(2RS)-3-[(1,1-Dimethylethyl)amino]-2-hydroxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol. It consists of 2 pairs of enantiomers that are present as 2 racemic compounds: racemate A and racemate B. Content 98.5 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white,…<\/p>\n","protected":false},"author":5,"featured_media":25548,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25547","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\/25547","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=25547"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25547\/revisions"}],"predecessor-version":[{"id":25672,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25547\/revisions\/25672"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25548"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25547"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25547"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25547"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time (min)<\/strong><\/td>\n	Mobile phase A (per cent V\/V)<\/strong><\/td>\n	Mobile phase B (per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 7<\/td>\n	77<\/td>\n	23<\/td>\n<\/tr>\n
7 – 30<\/td>\n	77 \u2192 65<\/td>\n	23 \u2192 35<\/td>\n<\/tr>\n
30 – 35<\/td>\n	65 \u2192 55<\/td>\n	35 \u2192 45<\/td>\n<\/tr>\n
35 – 55<\/td>\n	55<\/td>\n	45<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate<\/em>\u00a0 1 mL\/min.<\/p>\n Detection<\/em>\u00a0 Spectrophotometer at 206 nm.<\/p>\n Injection<\/em>\u00a0 20 \u00b5L.<\/p>\n Identification of impurities\u00a0<\/em> Use the chromatogram supplied with nadolol impurity mixture CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A and D.<\/p>\n Relative retention<\/em>\u00a0 With reference to nadolol (retention time = about 15 min): impurity A = about 0.2; impurity C (doublet) = about 0.47 and 0.53; impurity D = about 1.5.<\/p>\n System suitability\u00a0<\/em> Reference solution (b):<\/p>\n \u2014 resolution:<\/em> minimum 8.0 between the peaks due to nadolol and impurity D.<\/p>\n Limits:<\/em><\/p>\n \u2014 correction factor:<\/em> for the calculation of content, multiply the sum of the 2 peak areas of impurity C by 0.7;<\/p>\n \u2014 impurities A, C, D:<\/em> for each impurity, 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 unspecified impurities:<\/em> for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\n \u2014 total:<\/em> 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:<\/em> 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)<\/strong><\/p>\n Maximum 2.0 per cent, determined on 1.000 g by drying in vacuo at 60 \u00b0C for 3 h.<\/p>\n Sulfated ash (2.4.14)<\/strong><\/p>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n ASSAY<\/h2>\n Dissolve 0.250 g in 100 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).<\/p>\n l mL of 0.1 M perchloric acid is equivalent to 30.94 mg of C_{17<\/sub>H_{27<\/sub>NO_{4<\/sub>.<\/p>\n}}} IMPURITIES<\/h2>\n Specified impurities\u00a0 A, C, D.<\/em><\/p>\n Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10.<\/em><\/p>\n Control of impurities in substances for pharmaceutical use)\u00a0 B, E, F, G.<\/em><\/p>\n $\"Nadolol\"$ <\/p>\n A. cis-5-[(2RS)-2,3-dihydroxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol (tetraol),<\/p>\n $\"Nadolol\"$ <\/p>\n B. cis-5-[(2RS)-2-hydroxy-3-methoxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol,<\/p>\n $\"Nadolol\"$ <\/p>\n C. 5,5\u2032-[(2rs)-2-hydroxypropane-1,3-diylbis(oxy)]bis(cis-1,2,3,4-tetrahydronaphthalene-2,3-diol) (3 diastereoisomers),<\/p>\n $\"Nadolol\"$ <\/p>\n D. 5,5\u2032-[[(1,1-dimethylethyl)imino]bis[(2-hydroxypropane-1,3-diyl)oxy]]bis(cis-1,2,3,4- tetrahydronaphthalene-2,3-diol) (10 stereoisomers),<\/p>\n $\"Nadolol\"$ <\/p>\n E. cis-5-[(2RS)-3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-8-iodo-1,2,3,4-tetrahydronaphthalene-2,3-\u00a0 diol,<\/p>\n $\"Nadolol\"$ <\/p>\n F. (2RS)-1-[(1,1-dimethylethyl)amino]-3-(naphthalen-1-yloxy)propan-2-ol,<\/p>\n $\"Nadolol\"$ <\/p>\n G. (2RS)-1-[(1,1-dimethylethyl)amino]-3-[(5,6,7,8-tetrahydronaphthalen-1-yl)oxy]propan-2-ol.<\/p>\n \n Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Beta-adrenoceptor antagonist. Preparation Nadolol Oral Suspension Ph Eur DEFINITION cis-5-[(2RS)-3-[(1,1-Dimethylethyl)amino]-2-hydroxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol. It consists of 2 pairs of enantiomers that are present as 2 racemic compounds: racemate A and racemate B. Content 98.5 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white,…<\/p>\n","protected":false},"author":5,"featured_media":25548,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25547","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\/25547","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=25547"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25547\/revisions"}],"predecessor-version":[{"id":25672,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25547\/revisions\/25672"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25548"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25547"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25547"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25547"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

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

Solubility<\/h3>\nSlightly soluble in water, freely soluble in ethanol (96 per cent), practically insoluble in acetone.<\/p>\n

IDENTIFICATION<\/h2>\nInfrared absorption spectrophotometry (2.2.24).<\/p>\nComparison\u00a0 nadolol CRS.<\/p>\n

TESTS<\/h2>\n

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

Solubility<\/h3>\n
Slightly soluble in water, freely soluble in ethanol (96 per cent), practically insoluble in acetone.<\/p>\n

IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison\u00a0 nadolol CRS.<\/p>\n