{"id":23007,"date":"2025-10-31T10:06:01","date_gmt":"2025-10-31T03:06:01","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=23007"},"modified":"2025-10-31T10:06:01","modified_gmt":"2025-10-31T03:06:01","slug":"closantel-sodium-dihydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/closantel-sodium-dihydrate\/","title":{"rendered":"Closantel Sodium Dihydrate"},"content":{"rendered":"

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

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

Antihelminthic.<\/p>\n

Ph Eur<\/p>\n

\n
DEFINITION<\/h2>\n
N-[5-Chloro-4-[(RS)-(4-chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide sodium salt dihydrate.<\/p>\n
Content<\/strong><\/p>\n
98.5 per cent to 101.5 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/strong><\/p>\n
Yellow powder, slightly hygroscopic.<\/p>\n
Solubility<\/strong><\/p>\n
Very slightly soluble in water, freely soluble in ethanol (96 per cent), soluble in methanol. It shows polymorphism (5.9).<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24), without recrystallisation.<\/p>\n
Comparison<\/em>\u00a0 closantel sodium dihydrate CRS.<\/p>\n
B. Dissolve 0.1 g in 2 mL of ethanol (96 per cent) R. The solution gives reaction (a) of sodium (2.3.1).<\/p>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and not more intensely coloured than reference solution GY4 (2.2.2, Method II). Dissolve 0.50 g in ethanol (96 per cent) R and dilute to 50 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Prepare the solutions immediately before use and protect from light.<\/p>\n
Test solution<\/em> Dissolve 0.100 g of the substance to be examined in methanol R and dilute to 10.0 mL with the same solvent.<\/p>\n
Reference solution (a)<\/em>\u00a0 Dissolve 10 mg of closantel for system suitability CRS (containing impurities A to J) in methanol R and dilute to 1.0 mL with the same solvent.<\/p>\n
Reference solution (b)<\/em>\u00a0 Dilute 1.0 mL of the test solution to 100.0 mL with methanol R. Dilute 5.0 mL of this solution to 25.0 mL with methanol R.<\/p>\n
Column:<\/em><\/p>\n
\u2014 size: l<\/em> = 0.10 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase:<\/em> base-deactivated end-capped octadecylsilyl silica gel for chromatography R (3 \u00b5m);<\/p>\n
\u2014 temperature:<\/em> 35 \u00b0C.<\/p>\n
Mobile phase:<\/em><\/p>\n
\u2014 mobile phase A:<\/em> to 100 mL of a 7.7 g\/L solution of ammonium acetate R previously adjusted to pH 4.3 with acetic acid R, add 50 mL of acetonitrile for chromatography R and 850 mL of water for chromatography R;<\/p>\n
\u2014 mobile phase B:<\/em> to 100 mL of a 7.7 g\/L solution of ammonium acetate R previously adjusted to pH 4.3 with acetic acid R, add 50 mL of water for chromatography R and 850 mL of acetonitrile for chromatography R;<\/p>\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 – 2<\/td>\n 50<\/td>\n 50<\/td>\n<\/tr>\n
2 – 22<\/td>\n 50 \u2192 20<\/td>\n 50 \u2192 80<\/td>\n<\/tr>\n
22 – 27<\/td>\n 20<\/td>\n 80<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate<\/em>\u00a0 1.5 mL\/min.<\/p>\n
Detection<\/em>\u00a0 Spectrophotometer at 240 nm.<\/p>\n
Injection<\/em>\u00a0 10 \u00b5L.<\/p>\n
Identification of impurities<\/em> Use the chromatogram supplied with closantel for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities A, B, C, D, E, F, G, H, I and J.<\/p>\n
Relative retention<\/em>\u00a0 With reference to closantel (retention time = about 16 min): impurity A = about 0.07; impurity B = about 0.48; impurity C = about 0.62; impurity D = about 0.65; impurity E = about 0.82; impurity F = about 0.89; impurity G = about 0.93; impurity H = about 1.13; impurity I = about 1.16; impurity J = about 1.55.<\/p>\n
System suitability<\/em>\u00a0 Reference solution (a):<\/p>\n
\u2014 resolution:<\/em> baseline separation between the peaks due to impurity G and closantel;<\/p>\n
\u2014 the chromatogram obtained is similar to the chromatogram supplied with closantel for system suitability CRS.<\/p>\n
Limits:<\/em><\/p>\n
\u2014 correction factors:<\/em> for the calculation of contents, multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 1.5; impurity B = 1.3;<\/p>\n
\u2014 impurity G:<\/em> not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent);<\/p>\n
\u2014 impurities F, H, I:<\/em> for each impurity, not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);<\/p>\n
\u2014 impurities A, B, C, D, E, J:<\/em> for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (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 (b) (0.20 per cent);<\/p>\n
\u2014 total:<\/em> not more than 7.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (1.5 per cent);<\/p>\n
\u2014 disregard limit:<\/em> 0.25 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n
Water (2.5.12)<\/strong><\/p>\n
4.8 per cent to 5.8 per cent, determined on 0.250 g.<\/p>\n
Use a mixture of 1 volume of dimethylformamide R and 4 volumes of methanol R as the solvent.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.500 g in 50 mL of a mixture of 1 volume of anhydrous acetic acid R and 7 volumes of methyl ethyl ketone 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 68.5 mg of C_{22<\/sub>H_{13<\/sub>Cl_{2<\/sub>I_{2<\/sub>N_{2<\/sub>NaO_{2<\/sub>.<\/p>\n}}}}}}
STORAGE<\/h2>\n
In an airtight container, protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities\u00a0 A, B, C, D, E, F, G, H, I, J.<\/p>\n
$\"Closantel$ <\/p>\n
A. 2-hydroxy-3,5-diiodobenzoic acid,<\/p>\n
$\"Closantel$ <\/p>\n
B. (2RS)-(4-amino-2-chloro-5-methylphenyl)(4-chlorophenyl)ethanenitrile,<\/p>\n
$\"Closantel$ <\/p>\n
C. (2RS)-[2-chloro-4-[(2-hydroxy-3,5-diiodobenzoyl)amino]-5-methylphenyl](4-chlorophenyl)acetic acid,<\/p>\n
$\"Closantel$ <\/p>\n
D. N-[4-[(1RS)-2-amino-1-(4-chlorophenyl)-2-oxoethyl]-5-chloro-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide,<\/p>\n
$\"Closantel$ <\/p>\n
E. 3-chloro-N-[5-chloro-4-[(RS)-(4-chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-5-iodobenzamide,<\/p>\n
$\"Closantel$ <\/p>\n
F. N-[5-chloro-4-(4-chorobenzoyl)-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide,<\/p>\n
$\"Closantel$ <\/p>\n
G. methyl (2RS)-2-[2-chloro-4-[(2-hydroxy-3,5-diiodobenzoyl)amino]-5-methylphenyl]-2-(4-chlorophenyl)acetimidate,<\/p>\n
$\"Closantel$ <\/p>\n
H. methyl (2RS)-[2-chloro-4-[(2-hydroxy-3,5-diiodobenzoyl)amino]-5-methylphenyl](4-chlorophenyl)acetate,<\/p>\n
$\"Closantel$ <\/p>\n
I. N-[5-chloro-4-[(RS)-(4-chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-5-iodobenzamide,<\/p>\n
$\"Closantel$ <\/p>\n
J. N-[5-chloro-4-[[4-[[2-chloro-4-[(2-hydroxy-3,5-diiodobenzoyl)amino]-5-methylphenyl]cyanomethyl]phenyl](4- chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide.<\/p>\n
\n
Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":"
Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Antihelminthic. Ph Eur DEFINITION N-[5-Chloro-4-[(RS)-(4-chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide sodium salt dihydrate. Content 98.5 per cent to 101.5 per cent (anhydrous substance). CHARACTERS Appearance Yellow powder, slightly hygroscopic. Solubility Very slightly soluble in water, freely soluble in ethanol (96 per cent), soluble in methanol. It shows polymorphism (5.9). IDENTIFICATION…<\/p>\n","protected":false},"author":5,"featured_media":23008,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[176],"tags":[],"class_list":["post-23007","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-british-pharmacopoeia-veterinary-2020"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/23007","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=23007"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/23007\/revisions"}],"predecessor-version":[{"id":23035,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/23007\/revisions\/23035"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/23008"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=23007"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=23007"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=23007"}],"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 – 2<\/td>\n	50<\/td>\n	50<\/td>\n<\/tr>\n
2 – 22<\/td>\n	50 \u2192 20<\/td>\n	50 \u2192 80<\/td>\n<\/tr>\n
22 – 27<\/td>\n	20<\/td>\n	80<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate<\/em>\u00a0 1.5 mL\/min.<\/p>\n Detection<\/em>\u00a0 Spectrophotometer at 240 nm.<\/p>\n Injection<\/em>\u00a0 10 \u00b5L.<\/p>\n Identification of impurities<\/em> Use the chromatogram supplied with closantel for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities A, B, C, D, E, F, G, H, I and J.<\/p>\n Relative retention<\/em>\u00a0 With reference to closantel (retention time = about 16 min): impurity A = about 0.07; impurity B = about 0.48; impurity C = about 0.62; impurity D = about 0.65; impurity E = about 0.82; impurity F = about 0.89; impurity G = about 0.93; impurity H = about 1.13; impurity I = about 1.16; impurity J = about 1.55.<\/p>\n System suitability<\/em>\u00a0 Reference solution (a):<\/p>\n \u2014 resolution:<\/em> baseline separation between the peaks due to impurity G and closantel;<\/p>\n \u2014 the chromatogram obtained is similar to the chromatogram supplied with closantel for system suitability CRS.<\/p>\n Limits:<\/em><\/p>\n \u2014 correction factors:<\/em> for the calculation of contents, multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 1.5; impurity B = 1.3;<\/p>\n \u2014 impurity G:<\/em> not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent);<\/p>\n \u2014 impurities F, H, I:<\/em> for each impurity, not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);<\/p>\n \u2014 impurities A, B, C, D, E, J:<\/em> for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (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 (b) (0.20 per cent);<\/p>\n \u2014 total:<\/em> not more than 7.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (1.5 per cent);<\/p>\n \u2014 disregard limit:<\/em> 0.25 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n Water (2.5.12)<\/strong><\/p>\n 4.8 per cent to 5.8 per cent, determined on 0.250 g.<\/p>\n Use a mixture of 1 volume of dimethylformamide R and 4 volumes of methanol R as the solvent.<\/p>\n ASSAY<\/h2>\n Dissolve 0.500 g in 50 mL of a mixture of 1 volume of anhydrous acetic acid R and 7 volumes of methyl ethyl ketone 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 68.5 mg of C_{22<\/sub>H_{13<\/sub>Cl_{2<\/sub>I_{2<\/sub>N_{2<\/sub>NaO_{2<\/sub>.<\/p>\n}}}}}} STORAGE<\/h2>\n In an airtight container, protected from light.<\/p>\n IMPURITIES<\/h2>\n Specified impurities\u00a0 A, B, C, D, E, F, G, H, I, J.<\/p>\n $\"Closantel$ <\/p>\n A. 2-hydroxy-3,5-diiodobenzoic acid,<\/p>\n $\"Closantel$ <\/p>\n B. (2RS)-(4-amino-2-chloro-5-methylphenyl)(4-chlorophenyl)ethanenitrile,<\/p>\n $\"Closantel$ <\/p>\n C. (2RS)-[2-chloro-4-[(2-hydroxy-3,5-diiodobenzoyl)amino]-5-methylphenyl](4-chlorophenyl)acetic acid,<\/p>\n $\"Closantel$ <\/p>\n D. N-[4-[(1RS)-2-amino-1-(4-chlorophenyl)-2-oxoethyl]-5-chloro-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide,<\/p>\n $\"Closantel$ <\/p>\n E. 3-chloro-N-[5-chloro-4-[(RS)-(4-chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-5-iodobenzamide,<\/p>\n $\"Closantel$ <\/p>\n F. N-[5-chloro-4-(4-chorobenzoyl)-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide,<\/p>\n $\"Closantel$ <\/p>\n G. methyl (2RS)-2-[2-chloro-4-[(2-hydroxy-3,5-diiodobenzoyl)amino]-5-methylphenyl]-2-(4-chlorophenyl)acetimidate,<\/p>\n $\"Closantel$ <\/p>\n H. methyl (2RS)-[2-chloro-4-[(2-hydroxy-3,5-diiodobenzoyl)amino]-5-methylphenyl](4-chlorophenyl)acetate,<\/p>\n $\"Closantel$ <\/p>\n I. N-[5-chloro-4-[(RS)-(4-chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-5-iodobenzamide,<\/p>\n $\"Closantel$ <\/p>\n J. N-[5-chloro-4-[[4-[[2-chloro-4-[(2-hydroxy-3,5-diiodobenzoyl)amino]-5-methylphenyl]cyanomethyl]phenyl](4- chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide.<\/p>\n \n Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Antihelminthic. Ph Eur DEFINITION N-[5-Chloro-4-[(RS)-(4-chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide sodium salt dihydrate. Content 98.5 per cent to 101.5 per cent (anhydrous substance). CHARACTERS Appearance Yellow powder, slightly hygroscopic. Solubility Very slightly soluble in water, freely soluble in ethanol (96 per cent), soluble in methanol. It shows polymorphism (5.9). IDENTIFICATION…<\/p>\n","protected":false},"author":5,"featured_media":23008,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[176],"tags":[],"class_list":["post-23007","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-british-pharmacopoeia-veterinary-2020"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/23007","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=23007"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/23007\/revisions"}],"predecessor-version":[{"id":23035,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/23007\/revisions\/23035"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/23008"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=23007"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=23007"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=23007"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

DEFINITION<\/h2>\nN-[5-Chloro-4-[(RS)-(4-chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide sodium salt dihydrate.<\/p>\nContent<\/strong><\/p>\n98.5 per cent to 101.5 per cent (anhydrous substance).<\/p>\n

Appearance of solution<\/h3>\nThe solution is clear (2.2.1) and not more intensely coloured than reference solution GY4 (2.2.2, Method II). Dissolve 0.50 g in ethanol (96 per cent) R and dilute to 50 mL with the same solvent.<\/p>\n

STORAGE<\/h2>\nIn an airtight container, protected from light.<\/p>\n

DEFINITION<\/h2>\n
N-[5-Chloro-4-[(RS)-(4-chlorophenyl)cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide sodium salt dihydrate.<\/p>\n
Content<\/strong><\/p>\n
98.5 per cent to 101.5 per cent (anhydrous substance).<\/p>\n

Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and not more intensely coloured than reference solution GY4 (2.2.2, Method II). Dissolve 0.50 g in ethanol (96 per cent) R and dilute to 50 mL with the same solvent.<\/p>\n

STORAGE<\/h2>\n
In an airtight container, protected from light.<\/p>\n