{"id":1069,"date":"2025-09-18T10:14:54","date_gmt":"2025-09-18T03:14:54","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=1069"},"modified":"2025-10-01T15:58:17","modified_gmt":"2025-10-01T08:58:17","slug":"acemetacin","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/acemetacin\/","title":{"rendered":"Acemetacin"},"content":{"rendered":"

(Ph. Eur. monograph 1686)<\/p>\n

C_{21<\/sub>H_{18<\/sub>ClNO_{6<\/sub> 415.8 53164-05-9<\/p>\n}}}

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

Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.<\/p>\n

DEFINITION<\/h2>\n[[[1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetic 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
Yellow or greenish-yellow, crystalline powder.<\/p>\n
Solubility<\/h3>\n
Practically insoluble in water, soluble in acetone, slightly soluble in anhydrous ethanol.<\/p>\n
It shows polymorphism (5.9).<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison acemetacin CRS.<\/p>\n
If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substance separately in acetone R, evaporate to dryness and record new spectra using the residues.<\/p>\n
TESTS<\/h2>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Test solution: Dissolve 0.100 g of the substance to be examined in acetonitrile for chromatography R and dilute to 20.0 mL with the same solvent.<\/p>\n
Reference solution (a): Dilute 5.0 mL of the test solution to 50.0 mL with acetonitrile for chromatography R. Dilute 1.0 mL of this solution to 100.0 mL with acetonitrile for chromatography R.<\/p>\n
Reference solution (b): Dissolve 5.0 mg of acemetacin impurity A CRS and 10.0 mg of indometacin CRS (impurity B) in acetonitrile for chromatography R, and dilute to 50.0 mL with the same solvent.<\/p>\n
Reference solution (c): Dilute 1.0 mL of reference solution (b) to 20.0 mL with acetonitrile for chromatography R.<\/p>\n
Reference solution (d): To 1 mL of reference solution (b), add 10 mL of the test solution and dilute to 20 mL with acetonitrile for chromatography R.<\/p>\n
Reference solution (e): Dissolve the contents of a vial of acemetacin impurity mixture CRS (containing impurities C, D, E and F) in 1.0 mL of the test solution.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.25 m, \u00d8 = 4 mm;<\/p>\n
\u2014 stationary phase: spherical end-capped octadecylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: dissolve 1.0 g of potassium dihydrogen phosphate R in 900 mL of water R, adjust to pH 6.5 with 1 M sodium hydroxide and dilute to 1000 mL with water R;<\/p>\n
\u2014 mobile phase B: acetonitrile for chromatography R;<\/p>\n\n\n\n\n\n\n\n\n
Time
\n(min)<\/td>\n Mobile phase A
\n(per cent V\/V)<\/td>\n Mobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 5<\/td>\n 95<\/td>\n 5<\/td>\n<\/tr>\n
5 – 9<\/td>\n \u00a095 \u2192 65<\/td>\n \u00a05 \u2192 35<\/td>\n<\/tr>\n
9 – 16<\/td>\n 65<\/td>\n 35<\/td>\n<\/tr>\n
16 – 28<\/td>\n \u00a065 \u2192 20<\/td>\n \u00a035 \u2192 80<\/td>\n<\/tr>\n
28 – 34<\/td>\n 20<\/td>\n 80<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 235 nm.<\/p>\n
Injection: 20 \u03bcL.<\/p>\n
Identification of impurities:<\/p>\n
\u2014 use the chromatogram supplied with acemetacin impurity mixture CRS and the chromatogram obtained with reference solution (e) to identify the peaks due to impurities C, D, E and F;<\/p>\n
\u2014 use the chromatogram obtained with reference solution (b) to identify the peak due to impurity B.<\/p>\n
Relative retention: With reference to acemetacin (retention time = about 15 min): impurity A = about 0.7;
\nimpurity B = about 0.9; impurity F = about 1.2; impurity C = about 1.3; impurity D = about 1.5; impurity E = about 2.2.<\/p>\n
System suitability: Reference solution (d):<\/p>\n
\u2014 peak-to-valley ratio: minimum 15, where Hp = height above the baseline of the peak due to impurity B and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to acemetacin.<\/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 C = 1.3; impurity D = 1.4; impurity F = 1.3;<\/p>\n
\u2014 impurity E: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.3 per cent);<\/p>\n
\u2014 impurity B: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.2 per cent);<\/p>\n
\u2014 impurity A: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.1 per cent);<\/p>\n
\u2014 impurities C, D, F: for each 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 unspecified impurities: 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: not more than 4 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.4 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 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.350 g in 20 mL of acetone R and add 10 mL of water R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).<\/p>\n
1 mL of 0.1 M sodium hydroxide is equivalent to 41.58 mg of C_{21<\/sub>H_{18<\/sub>ClNO_{6<\/sub>.<\/p>\n}}}
STORAGE<\/h2>\n
Protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities A, B, C, D, E, F.<\/p>\n
$\"Acemetacin-1\"$ <\/p>\n
A. 4-chlorobenzoic acid,<\/p>\n
$\"Acemetacin-2\"$ <\/p>\n
B. [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (indometacin),<\/p>\n
$\"Acemetacin-3\"$ <\/p>\n
C. [[[1-(3,4-dichlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetic acid,<\/p>\n
$\"Acemetacin-4\"$ <\/p>\n
D. [[[1-(4-chlorobenzoyl)-6-(1,1-dimethylethyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetic acid,<\/p>\n
$\"Acemetacin-5\"$ <\/p>\n
E. 1,1-dimethylethyl [[[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetate,<\/p>\n
$\"Acemetacin-6\"$ <\/p>\n
F. [[[[[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetyl]oxy]acetic acid.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 1686) C21H18ClNO6 415.8 53164-05-9 Action and use Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory. DEFINITION [[[1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetic acid. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance Yellow or greenish-yellow, crystalline powder. Solubility Practically insoluble in water, soluble in acetone, slightly soluble in anhydrous ethanol. It shows polymorphism (5.9). IDENTIFICATION Infrared absorption spectrophotometry…<\/p>\n","protected":false},"author":3,"featured_media":1074,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-1069","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\/1069","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=1069"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1069\/revisions"}],"predecessor-version":[{"id":6706,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1069\/revisions\/6706"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/1074"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=1069"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=1069"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=1069"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time \n(min)<\/td>\n	Mobile phase A \n(per cent V\/V)<\/td>\n	Mobile phase B \n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 5<\/td>\n	95<\/td>\n	5<\/td>\n<\/tr>\n
5 – 9<\/td>\n	\u00a095 \u2192 65<\/td>\n	\u00a05 \u2192 35<\/td>\n<\/tr>\n
9 – 16<\/td>\n	65<\/td>\n	35<\/td>\n<\/tr>\n
16 – 28<\/td>\n	\u00a065 \u2192 20<\/td>\n	\u00a035 \u2192 80<\/td>\n<\/tr>\n
28 – 34<\/td>\n	20<\/td>\n	80<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 1.0 mL\/min.<\/p>\n Detection: Spectrophotometer at 235 nm.<\/p>\n Injection: 20 \u03bcL.<\/p>\n Identification of impurities:<\/p>\n \u2014 use the chromatogram supplied with acemetacin impurity mixture CRS and the chromatogram obtained with reference solution (e) to identify the peaks due to impurities C, D, E and F;<\/p>\n \u2014 use the chromatogram obtained with reference solution (b) to identify the peak due to impurity B.<\/p>\n Relative retention: With reference to acemetacin (retention time = about 15 min): impurity A = about 0.7; \nimpurity B = about 0.9; impurity F = about 1.2; impurity C = about 1.3; impurity D = about 1.5; impurity E = about 2.2.<\/p>\n System suitability: Reference solution (d):<\/p>\n \u2014 peak-to-valley ratio: minimum 15, where Hp = height above the baseline of the peak due to impurity B and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to acemetacin.<\/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 C = 1.3; impurity D = 1.4; impurity F = 1.3;<\/p>\n \u2014 impurity E: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.3 per cent);<\/p>\n \u2014 impurity B: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.2 per cent);<\/p>\n \u2014 impurity A: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.1 per cent);<\/p>\n \u2014 impurities C, D, F: for each 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 unspecified impurities: 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: not more than 4 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.4 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 1.0 g.<\/p>\n ASSAY<\/h2>\n Dissolve 0.350 g in 20 mL of acetone R and add 10 mL of water R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).<\/p>\n 1 mL of 0.1 M sodium hydroxide is equivalent to 41.58 mg of C_{21<\/sub>H_{18<\/sub>ClNO_{6<\/sub>.<\/p>\n}}} STORAGE<\/h2>\n Protected from light.<\/p>\n IMPURITIES<\/h2>\n Specified impurities A, B, C, D, E, F.<\/p>\n $\"Acemetacin-1\"$ <\/p>\n A. 4-chlorobenzoic acid,<\/p>\n $\"Acemetacin-2\"$ <\/p>\n B. [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (indometacin),<\/p>\n $\"Acemetacin-3\"$ <\/p>\n C. [[[1-(3,4-dichlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetic acid,<\/p>\n $\"Acemetacin-4\"$ <\/p>\n D. [[[1-(4-chlorobenzoyl)-6-(1,1-dimethylethyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetic acid,<\/p>\n $\"Acemetacin-5\"$ <\/p>\n E. 1,1-dimethylethyl [[[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetate,<\/p>\n $\"Acemetacin-6\"$ <\/p>\n F. [[[[[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetyl]oxy]acetic acid.<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 1686) C21H18ClNO6 415.8 53164-05-9 Action and use Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory. DEFINITION [[[1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl]oxy]acetic acid. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance Yellow or greenish-yellow, crystalline powder. Solubility Practically insoluble in water, soluble in acetone, slightly soluble in anhydrous ethanol. It shows polymorphism (5.9). IDENTIFICATION Infrared absorption spectrophotometry…<\/p>\n","protected":false},"author":3,"featured_media":1074,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-1069","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\/1069","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=1069"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1069\/revisions"}],"predecessor-version":[{"id":6706,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1069\/revisions\/6706"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/1074"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=1069"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=1069"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=1069"}],"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>\nYellow or greenish-yellow, crystalline powder.<\/p>\n

Solubility<\/h3>\nPractically insoluble in water, soluble in acetone, slightly soluble in anhydrous ethanol.<\/p>\nIt shows polymorphism (5.9).<\/p>\n

TESTS<\/h2>\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 1.0 g.<\/p>\n

ASSAY<\/h2>\nDissolve 0.350 g in 20 mL of acetone R and add 10 mL of water R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).<\/p>\n1 mL of 0.1 M sodium hydroxide is equivalent to 41.58 mg of C21<\/sub>H18<\/sub>ClNO6<\/sub>.<\/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
Yellow or greenish-yellow, crystalline powder.<\/p>\n

Solubility<\/h3>\n
Practically insoluble in water, soluble in acetone, slightly soluble in anhydrous ethanol.<\/p>\n
It shows polymorphism (5.9).<\/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 1.0 g.<\/p>\n

ASSAY<\/h2>\n
Dissolve 0.350 g in 20 mL of acetone R and add 10 mL of water R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).<\/p>\n
1 mL of 0.1 M sodium hydroxide is equivalent to 41.58 mg of C_{21<\/sub>H_{18<\/sub>ClNO_{6<\/sub>.<\/p>\n}}}

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