{"id":4646,"date":"2025-09-27T11:11:52","date_gmt":"2025-09-27T04:11:52","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=4646"},"modified":"2025-10-02T15:55:49","modified_gmt":"2025-10-02T08:55:49","slug":"capecitabine","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/capecitabine\/","title":{"rendered":"Capecitabine"},"content":{"rendered":"

(Ph. Eur. monograph 2762)<\/p>\n

C_{15<\/sub>H_{22<\/sub>FN_{3<\/sub>O_{6<\/sub>\u00a0 \u00a0 \u00a0 \u00a0 359.3\u00a0 \u00a0 \u00a0 \u00a0154361-50-9<\/p>\n}}}}

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

Pyrimidine analogue; cytotoxic; treatment of colorectal cancer.<\/p>\n

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

Capecitabine Tablets<\/p>\n

DEFINITION<\/h2>\n
Pentyl [1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate.<\/p>\n
Content<\/h3>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h3>\n
Appearance<\/h3>\n
White or almost white powder.<\/p>\n
Solubility<\/h3>\n
Sparingly soluble in water, freely soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\n
IDENTIFICATION<\/h2>\n
A. Specific optical rotation (see Tests).<\/p>\n
B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: capecitabine CRS.<\/p>\n
TESTS<\/h2>\n
Specific optical rotation (2.2.7)<\/h3>\n
+ 96.0 to + 100.0 (anhydrous substance).<\/p>\n
Dissolve 0.250 g in methanol R and dilute to 25.0 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Prepare the solutions immediately before use or store them at 2-8 \u00b0C.<\/p>\n
Solvent mixture: acetonitrile R, methanol R, water R (5:35:60 V\/V\/V).<\/p>\n
Test solution: Dissolve 60.0 mg of the substance to be examined in 80 mL of the solvent mixture, sonicate until dissolution is complete and dilute to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (a): Dissolve 60.0 mg of capecitabine CRS in 80 mL of the solvent mixture, sonicate until dissolution is complete and dilute to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (b): Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 20.0 mL with the solvent mixture.<\/p>\n
Reference solution (c): Dissolve 3 mg of capecitabine impurity A CRS, 3 mg of capecitabine impurity B CRS and 5 mg of capecitabine impurity D CRS in 80 mL of the solvent mixture, sonicate until dissolution is complete and dilute to 100.0 mL with the solvent mixture. Dilute 1 mL of the solution to 50 mL with the test solution.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: 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: acetonitrile R, methanol R, 0.1 per cent V\/V solution of glacial acetic acid R (5:35:60 V\/V\/V);<\/p>\n
\u2014 mobile phase B: acetonitrile R, 0.1 per cent V\/V solution of glacial acetic acid R, methanol R (5:15:80 V\/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 – 5<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
5 – 20<\/td>\n 100 \u2192 49<\/td>\n 0 \u2192 51<\/td>\n<\/tr>\n
20 – 30<\/td>\n 49<\/td>\n 51<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 250 nm.<\/p>\n
Injection: 10 \u03bcL of the test solution and reference solutions (b) and (c).<\/p>\n
Identification of impurities: Use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A, B and D.<\/p>\n
Relative retention: With reference to capecitabine (retention time = about 17 min): impurity A = about 0.18; impurity B = about 0.19; impurities D and E = about 0.95.<\/p>\n
System suitability: Reference solution (c):<\/p>\n
\u2014 resolution: minimum 1.5 between the peaks due to impurities A and B; minimum 2.0 between the peaks due to impurity D and capecitabine.<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of capecitabine in reference solution (b);<\/p>\n
\u2014 correction factor: multiply the peak area of impurity B by 1.3.<\/p>\n
Limits:<\/p>\n
\u2014 impurities A, B: for each impurity, maximum 0.3 per cent;<\/p>\n
\u2014 sum of impurities D and E: maximum 0.2 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.05 per cent;<\/p>\n
\u2014 total: maximum 0.5 per cent;<\/p>\n
\u2014 reporting threshold: 0.03 per cent.<\/p>\n
Water (2.5.32)<\/h4>\n
Maximum 0.3 per cent.<\/p>\n
Inject 1.0 mL of a 0.200 g\/mL solution of the substance to be examined in methanol R.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g in a platinum crucible.<\/p>\n
ASSAY<\/h2>\n
Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n
Injection: Test solution and reference solution (a).<\/p>\n
Calculate the percentage content of C_{15<\/sub>H_{22<\/sub>FN_{3<\/sub>O_{6<\/sub> taking into account the assigned content of capecitabine CRS.<\/p>\n}}}}
IMPURITIES<\/h2>\n
Specified impurities: A, B, D, E.<\/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. Control of impurities in substances for pharmaceutical use) C, F, G.<\/p>\n
$\"Capecitabine\"$ <\/p>\n
A. 4-amino-1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoropyrimidin-2(1H)-one (5\u02b9-deoxy-5-fluorocytidine),<\/p>\n
$\"Capecitabine\"$ <\/p>\n
B. 1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoropyrimidine-2,4(1H,3H)-dione (5\u02b9-deoxy-5-fluorouridine),<\/p>\n
$\"Capecitabine\"$ <\/p>\n
C. 1-(2,3-di-O-acetyl-5-deoxy-\u03b2-D-ribofuranosyl)-4-amino-5-fluoropyrimidin-2(1H)-one,<\/p>\n
$\"Capecitabine\"$ <\/p>\n
D. (2RS)-2-methylbutyl [1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate,<\/p>\n
$\"Capecitabine\"$ <\/p>\n
E. 3-methylbutyl [1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate,<\/p>\n
$\"Capecitabine\"$ <\/p>\n
F. pentyl [5-fluoro-1-[(3aR,4R,6R,6aR)-6-methyl-2-oxotetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate,<\/p>\n
$\"Capecitabine\"$ <\/p>\n
G. pentyl [1-(2,3-di-O-acetyl-5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 2762) C15H22FN3O6\u00a0 \u00a0 \u00a0 \u00a0 359.3\u00a0 \u00a0 \u00a0 \u00a0154361-50-9 Action and use Pyrimidine analogue; cytotoxic; treatment of colorectal cancer. Preparation Capecitabine Tablets DEFINITION Pentyl [1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate. Content 98.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white powder. Solubility Sparingly soluble in water, freely soluble in anhydrous ethanol,…<\/p>\n","protected":false},"author":2,"featured_media":4692,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-4646","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\/4646","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=4646"}],"version-history":[{"count":6,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/4646\/revisions"}],"predecessor-version":[{"id":7965,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/4646\/revisions\/7965"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/4692"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=4646"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=4646"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=4646"}],"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 – 5<\/td>\n	100<\/td>\n	0<\/td>\n<\/tr>\n
5 – 20<\/td>\n	100 \u2192 49<\/td>\n	0 \u2192 51<\/td>\n<\/tr>\n
20 – 30<\/td>\n	49<\/td>\n	51<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 1.0 mL\/min.<\/p>\n Detection: Spectrophotometer at 250 nm.<\/p>\n Injection: 10 \u03bcL of the test solution and reference solutions (b) and (c).<\/p>\n Identification of impurities: Use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A, B and D.<\/p>\n Relative retention: With reference to capecitabine (retention time = about 17 min): impurity A = about 0.18; impurity B = about 0.19; impurities D and E = about 0.95.<\/p>\n System suitability: Reference solution (c):<\/p>\n \u2014 resolution: minimum 1.5 between the peaks due to impurities A and B; minimum 2.0 between the peaks due to impurity D and capecitabine.<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 for each impurity, use the concentration of capecitabine in reference solution (b);<\/p>\n \u2014 correction factor: multiply the peak area of impurity B by 1.3.<\/p>\n Limits:<\/p>\n \u2014 impurities A, B: for each impurity, maximum 0.3 per cent;<\/p>\n \u2014 sum of impurities D and E: maximum 0.2 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.05 per cent;<\/p>\n \u2014 total: maximum 0.5 per cent;<\/p>\n \u2014 reporting threshold: 0.03 per cent.<\/p>\n Water (2.5.32)<\/h4>\n Maximum 0.3 per cent.<\/p>\n Inject 1.0 mL of a 0.200 g\/mL solution of the substance to be examined in methanol R.<\/p>\n Sulfated ash (2.4.14)<\/h4>\n Maximum 0.1 per cent, determined on 1.0 g in a platinum crucible.<\/p>\n ASSAY<\/h2>\n Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n Injection: Test solution and reference solution (a).<\/p>\n Calculate the percentage content of C_{15<\/sub>H_{22<\/sub>FN_{3<\/sub>O_{6<\/sub> taking into account the assigned content of capecitabine CRS.<\/p>\n}}}} IMPURITIES<\/h2>\n Specified impurities: A, B, D, E.<\/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. Control of impurities in substances for pharmaceutical use) C, F, G.<\/p>\n $\"Capecitabine\"$ <\/p>\n A. 4-amino-1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoropyrimidin-2(1H)-one (5\u02b9-deoxy-5-fluorocytidine),<\/p>\n $\"Capecitabine\"$ <\/p>\n B. 1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoropyrimidine-2,4(1H,3H)-dione (5\u02b9-deoxy-5-fluorouridine),<\/p>\n $\"Capecitabine\"$ <\/p>\n C. 1-(2,3-di-O-acetyl-5-deoxy-\u03b2-D-ribofuranosyl)-4-amino-5-fluoropyrimidin-2(1H)-one,<\/p>\n $\"Capecitabine\"$ <\/p>\n D. (2RS)-2-methylbutyl [1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate,<\/p>\n $\"Capecitabine\"$ <\/p>\n E. 3-methylbutyl [1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate,<\/p>\n $\"Capecitabine\"$ <\/p>\n F. pentyl [5-fluoro-1-[(3aR,4R,6R,6aR)-6-methyl-2-oxotetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate,<\/p>\n $\"Capecitabine\"$ <\/p>\n G. pentyl [1-(2,3-di-O-acetyl-5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate.<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 2762) C15H22FN3O6\u00a0 \u00a0 \u00a0 \u00a0 359.3\u00a0 \u00a0 \u00a0 \u00a0154361-50-9 Action and use Pyrimidine analogue; cytotoxic; treatment of colorectal cancer. Preparation Capecitabine Tablets DEFINITION Pentyl [1-(5-deoxy-\u03b2-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate. Content 98.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white powder. Solubility Sparingly soluble in water, freely soluble in anhydrous ethanol,…<\/p>\n","protected":false},"author":2,"featured_media":4692,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-4646","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\/4646","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=4646"}],"version-history":[{"count":6,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/4646\/revisions"}],"predecessor-version":[{"id":7965,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/4646\/revisions\/7965"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/4692"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=4646"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=4646"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=4646"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h3>\n

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

Solubility<\/h3>\nSparingly soluble in water, freely soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\n

IDENTIFICATION<\/h2>\nA. Specific optical rotation (see Tests).<\/p>\nB. Infrared absorption spectrophotometry (2.2.24).<\/p>\nComparison: capecitabine CRS.<\/p>\n

TESTS<\/h2>\n

Specific optical rotation (2.2.7)<\/h3>\n+ 96.0 to + 100.0 (anhydrous substance).<\/p>\nDissolve 0.250 g in methanol R and dilute to 25.0 mL with the same solvent.<\/p>\n

Water (2.5.32)<\/h4>\nMaximum 0.3 per cent.<\/p>\nInject 1.0 mL of a 0.200 g\/mL solution of the substance to be examined in methanol R.<\/p>\n

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

Content<\/h3>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

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

Solubility<\/h3>\n
Sparingly soluble in water, freely soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\n

IDENTIFICATION<\/h2>\n
A. Specific optical rotation (see Tests).<\/p>\n
B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: capecitabine CRS.<\/p>\n

Specific optical rotation (2.2.7)<\/h3>\n
+ 96.0 to + 100.0 (anhydrous substance).<\/p>\n
Dissolve 0.250 g in methanol R and dilute to 25.0 mL with the same solvent.<\/p>\n

Water (2.5.32)<\/h4>\n
Maximum 0.3 per cent.<\/p>\n
Inject 1.0 mL of a 0.200 g\/mL solution of the substance to be examined in methanol R.<\/p>\n

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