{"id":14332,"date":"2025-10-15T10:41:53","date_gmt":"2025-10-15T03:41:53","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=14332"},"modified":"2025-10-15T10:41:53","modified_gmt":"2025-10-15T03:41:53","slug":"etoposide","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/etoposide\/","title":{"rendered":"Etoposide"},"content":{"rendered":"

(Ph. Eur. monograph 0823)<\/em><\/p>\n

C29<\/sub>H32<\/sub>O13<\/sub> 588.6 33419-42-0<\/p>\n

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

Inhibitor of DNA topoisomerase type II; cytotoxic.<\/p>\n

Preparations<\/strong><\/p>\n

Etoposide Capsules<\/p>\n

Etoposide Infusion<\/p>\n

Etoposide Oral Solution<\/p>\n

DEFINITION<\/h2>\n

(5R,5aR,8aR,9S)-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-\u03b2-D-glucopyranosyl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9- tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one.<\/p>\n

Content<\/h3>\n

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

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

White or almost white, crystalline powder, slightly hygroscopic.<\/p>\n

Solubility<\/h3>\n

Practically insoluble in water, sparingly soluble in methanol, slightly soluble in ethanol (96 per cent) and in methylene chloride.<\/p>\n

IDENTIFICATION<\/h2>\n

First identification: A, B.<\/p>\n

Second identification: C, D.<\/p>\n

A. Specific optical rotation (see Tests).<\/p>\n

B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n

Comparison: etoposide CRS.<\/p>\n

C. Thin-layer chromatography (2.2.27).<\/p>\n

Test solution: Dissolve 10 mg of the substance to be examined in a mixture of 1 volume of methanol R and 9 volumes of methylene chloride R and dilute to 2 mL with the same mixture of solvents.<\/p>\n

Reference solution: Dissolve 10 mg of etoposide CRS in a mixture of 1 volume of methanol R and 9 volumes of methylene chloride R and dilute to 2 mL with the same mixture of solvents.<\/p>\n

Plate: silica gel H R as the coating substance.<\/p>\n

Mobile phase: water R, glacial acetic acid R, acetone R, methylene chloride R (1.5:8:20:100 V\/V\/V\/V).<\/p>\n

Application: 5 \u03bcL as bands of 10 mm.<\/p>\n

Development: Immediately, over 6\/7 of the plate.<\/p>\n

Drying: In a current of warm air for 5 min.<\/p>\n

Detection: Spray with a mixture of 1 volume of sulfuric acid R and 9 volumes of ethanol (96 per cent) R and heat at 140 \u00b0C for 15 min. Cover the plate immediately with a glass plate of the same size. Examine in daylight.<\/p>\n

Results The principal zone in the chromatogram obtained with the test solution is similar in position, colour and size to the principal zone in the chromatogram obtained with the reference solution.<\/p>\n

D. In a test-tube dissolve about 5 mg in 5 mL of glacial acetic acid R and add 0.05 mL of ferric chloride solution R1. Mix and cautiously add 2 mL of sulfuric acid R. Avoid mixing the 2 layers. Allow to stand for about 30 min; a pink to reddish-brown ring develops at the interface and the upper layer is yellow.<\/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 Y6<\/sub> or BY6 <\/sub>(2.2.2, Method II).<\/p>\n

Dissolve 0.6 g in a mixture of 1 volume of methanol R and 9 volumes of methylene chloride R and dilute to 20 mL with the same mixture of solvents.<\/p>\n

Specific optical rotation (2.2.7)<\/h3>\n

-114 to -106 (anhydrous substance).<\/p>\n

Dissolve 50.0 mg in a mixture of 1 volume of methanol R and 9 volumes of methylene chloride R and dilute to 10.0 mL with the same mixture of solvents.<\/p>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29).<\/p>\n

Solvent mixture: Mobile phase A, mobile phase B (50:50 V\/V).<\/p>\n

Test solution (a): Dissolve 40 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n

Test solution (b): Dissolve 50.0 mg of the substance to be examined in the solvent mixture and dilute to 50.0 mL with the solvent mixture.<\/p>\n

Reference solution (a): Dilute 1.0 mL of test solution (a) 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 4 mg of etoposide for system suitability CRS (containing impurities B, C, D, E, N and O) in 1.0 mL of the solvent mixture.<\/p>\n

Reference solution (c): Dissolve 50.0 mg of etoposide CRS in the solvent mixture and dilute to 50.0 mL with the solvent mixture.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.125 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: anhydrous formic acid R, triethylamine R, water for chromatography R (1:1:998 V\/V\/V);<\/p>\n

\u2014 mobile phase B: anhydrous formic acid R, triethylamine R, acetonitrile R (1:1:998 V\/V\/V);<\/p>\n\n\n\n\n\n
Time<\/strong><\/p>\n

(min)<\/strong><\/td>\n

Mobile phase A<\/strong><\/p>\n

(per cent V\/V)<\/strong><\/td>\n

Mobile phase B<\/strong><\/p>\n

(per cent V\/V)<\/strong><\/td>\n<\/tr>\n

0 – 7<\/td>\n75<\/td>\n25<\/td>\n<\/tr>\n
7 – 23<\/td>\n75 \u2192 27<\/td>\n25 \u2192 73<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Flow rate: 1 mL\/min.<\/p>\n

Detection: Spectrophotometer at 285 nm.<\/p>\n

Injection: 10 \u03bcL of test solution (a) and reference solutions (a) and (b).<\/p>\n

Identification of impurities: Use the chromatogram supplied with etoposide for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities B, C, D, E, N and O.<\/p>\n

Relative retention: With reference to etoposide (retention time = about 5 min): impurity D = about 0.4; impurity E = about 0.8; impurity C = about 1.1; impurity B = about 1.2; impurity N = about 3.1; impurity O = about 4.2.<\/p>\n

System suitability: Reference solution (b):<\/p>\n

\u2014 peak-to-valley ratio: minimum 2.0, where Hp = height above the baseline of the peak due to impurity C and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to etoposide; and minimum 3.0, where Hp = height above the baseline of the peak due to impurity B and Hv = height above the
\nbaseline of the lowest point of the curve separating this peak from the peak due to impurity C.<\/p>\n

Limits:<\/p>\n

\u2014 correction factor: for the calculation of content, multiply the peak area of impurity O by 1.7;<\/p>\n

\u2014 impurities B, C, D, E, N: 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 impurity O: not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.15 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 10 times the area of the principal peak in the chromatogram obtained with reference solution (a) (1.0 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); disregard any peak due to the solvent.<\/p>\n

Water<\/h3>\n

(2.5.32)Maximum 6.0 per cent, determined on 0.150 g using the evaporation technique at 130 \u00b0C.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\n

Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n

Liquid chromatography (2.2.29) as described in the test for related substances with the following modifications.<\/p>\n

Injection: Test solution (b) and reference solution (c).<\/p>\n

System suitability:<\/p>\n

\u2014 repeatability: maximum relative standard deviation of 1.0 per cent determined on 6 injections of reference solution (c).<\/p>\n

Calculate the percentage content of C29<\/sub>H32<\/sub>O13<\/sub> taking into account the assigned content of etoposide CRS.<\/p>\n

STORAGE<\/h2>\n

In an airtight container.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities B, C, D, E, N, O.<\/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) A, F, G, H, I, J, K, L, M, P, Q, R.<\/p>\n

\"Etoposide<\/p>\n

A. (5R,5aR,8aR,9S)-5-[4-[[(benzyloxy)carbonyl]oxy]-3,5-dimethoxyphenyl]-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-\u03b2-D- glucopyranosyl]oxy]-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4′-carbobenzoyloxyethylidene-lignan P),<\/p>\n

\"Etoposide<\/p>\n

B. (5R,5aS,8aR,9S)-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-\u03b2-D-glucopyranosyl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (picroethylidene-lignan P; cis-etoposide),<\/p>\n

\"Etoposide<\/p>\n

C. (5R,5aR,8aR,9S)-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-\u03b1-D-glucopyranosyl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (\u03b1-etoposide),<\/p>\n

\"Etoposide<\/p>\n

D. (5R,5aR,8aR,9S)-9-(\u03b2-D-glucopyranosyloxy)-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro-[5,6-f][1,3]benzodioxol-6(5aH)-one (lignan P),<\/p>\n

\"Etoposide<\/p>\n

E. (5R,5aR,8aR,9S)-9-hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4\u2032-desmethylepipodophyllotoxin),<\/p>\n

\"Etoposide<\/p>\n

F. (5R,5aR,8aR,9S)-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-\u03b2-D-glucopyranosyl]oxy]-5-[4-[(phenoxyacetyl)oxy]-3,5-dimethoxyphenyl]-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4′-phenoxyacetyletoposide),<\/p>\n

\"Etoposide<\/p>\n

G. (5R,5aR,8aR,9S)-5-[4-[[(benzyloxy)carbonyl]oxy]-3,5-dimethoxyphenyl]-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-2,3-di-O-formyl-\u03b2-D-glucopyranosyl]oxy]-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4′-carbobenzoyloxydiformyl-ethylidene-lignan P),<\/p>\n

\"Etoposide<\/p>\n

H. (5R,5aR,8aR,9S)-9-ethoxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4\u2032-O-desmethyl-1-O ethylepipodophyllotoxin),<\/p>\n

\"Etoposide<\/p>\n

I. (5R,5aR,8aR,9S)-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-\u03b2-D-glucopyranosyl]oxy]-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4-O-methylethylidene-lignan P),<\/p>\n

\"Etoposide<\/p>\n

J. (5R,5aR,8aR,9S)-5-(4-hydroxy-3,5-dimethoxyphenyl)-9-methoxy-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4\u2032-O-desmethyl-1-O-methylepipodophyllotoxin),<\/p>\n

\"Etoposide<\/p>\n

K. 9,9\u2032-oxybis[(5R,5aR,8aR,9S)-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro-[5,6-f][1,3]benzodioxol-6(5aH)-one] (di-4\u2032-O-desmethylepipodophyllotoxin),<\/p>\n

\"Etoposide<\/p>\n

L. (5R,5aR,8aR,9R)-9-hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4\u2032-O-desmethylpodophyllotoxin),<\/p>\n

\"Etoposide<\/p>\n

M. (5R,5aR,8aR,9R)-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (podophyllotoxin),<\/p>\n

\"Etoposide<\/p>\n

N. (5R,5aR,8aR,9S)-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-\u03b2-D-glucopyranosyl]oxy]-5-[4-[[(5R,5aR,8aR,9S)-5-(4-hydroxy-3,5-dimethoxyphenyl)-6-oxo-5,5a,6,8,8a,9-hexahydro[2]benzofuro[5,6-f][1,3]benzodioxol-9-yl]oxy]-3,5- dimethoxyphenyl]-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one,<\/p>\n

\"Etoposide<\/p>\n

O. (5R,5aR,8aR,9S)-9-[[2,3-bis-O-(dichloroacetyl)-4,6-O-[(1S)-ethane-1,1-diyl]-\u03b2-L-glucopyranosyl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one,<\/p>\n

\"Etoposide<\/p>\n

P. 9-hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)[2]benzofuro[5,6-f][1,3]benzodioxol-6(8H)-one,<\/p>\n

\"Etoposide<\/p>\n

Q. 5-(4-hydroxy-3,5-dimethoxyphenyl)[2]benzofuro[5,6-f][1,3]benzodioxol-6(8H)-one,<\/p>\n

\"Etoposide<\/p>\n

R. (5R,5aR,8aR,9S)-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-\u03b2-D-glucopyranosyl]oxy]-5-[4-[[(5R,5aR,8aR,9R)-5-(4-hydroxy-3,5-dimethoxyphenyl)-6-oxo-5,5a,6,8,8a,9-hexahydro[2]benzofuro[5,6-f][1,3]benzodioxol-9-yl]oxy]-3,5-dimethoxyphenyl]-5,8,8a,9-tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one.<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 0823) C29H32O13 588.6 33419-42-0 Action and use Inhibitor of DNA topoisomerase type II; cytotoxic. Preparations Etoposide Capsules Etoposide Infusion Etoposide Oral Solution DEFINITION (5R,5aR,8aR,9S)-9-[[4,6-O-[(1R)-ethane-1,1-diyl]-\u03b2-D-glucopyranosyl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9- tetrahydro[2]benzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one. Content 98.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, crystalline powder, slightly hygroscopic. Solubility Practically insoluble in water, sparingly soluble…<\/p>\n","protected":false},"author":4,"featured_media":14372,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-14332","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\/14332","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=14332"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/14332\/revisions"}],"predecessor-version":[{"id":14408,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/14332\/revisions\/14408"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/14372"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=14332"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=14332"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=14332"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}