{"id":11118,"date":"2025-10-09T09:44:20","date_gmt":"2025-10-09T02:44:20","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=11118"},"modified":"2025-10-09T09:44:20","modified_gmt":"2025-10-09T02:44:20","slug":"estradiol-hemihydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/estradiol-hemihydrate\/","title":{"rendered":"Estradiol Hemihydrate"},"content":{"rendered":"

(Ph. Eur. monograph 0821)<\/p>\n

C18<\/sub>H24<\/sub>O2<\/sub>,1<\/sup>\u20442<\/sub>H2<\/sub>O\u00a0 \u00a0281.4<\/p>\n

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

Estrogen.<\/p>\n

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

Estradiol Tablets<\/p>\n

Estradiol Transdermal Patches<\/p>\n

Estradiol and Norethisterone Tablets<\/p>\n

Estradiol and Norethisterone Acetate Tablets<\/p>\n

Estradiol Vaginal Tablets<\/p>\n

DEFINITION<\/h2>\n

Estra-1,3,5(10)-triene-3,17\u03b2-diol hemihydrate.<\/p>\n

Content<\/h3>\n

97.0 per cent to 103.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

White or almost white, crystalline powder or colourless crystals.<\/p>\n

Solubility<\/h3>\n

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

IDENTIFICATION<\/h2>\n

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

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

A. Melting point (2.2.14): 175 \u00b0C to 180 \u00b0C.<\/p>\n

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

Comparison estradiol hemihydrate CRS.<\/p>\n

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

Test solution: Dissolve 50 mg of the substance to be examined in methanol R and dilute to 50 mL with the same solvent.<\/p>\n

Reference solution (a): Dissolve 50 mg of estradiol hemihydrate CRS in methanol R and dilute to 50 mL with the same solvent.<\/p>\n

Reference solution (b): Dissolve 25 mg of ethinylestradiol CRS in reference solution (a) and dilute to 25 mL with reference solution (a).<\/p>\n

Plate TLC silica gel plate R.<\/p>\n

Mobile phase ethanol (96 per cent) R, toluene R (20:80 V\/V).<\/p>\n

Application 5 \u03bcL.<\/p>\n

Development Over 3\/4 of the plate.<\/p>\n

Drying In air until the solvent has evaporated.<\/p>\n

Detection Heat at 110 \u00b0C for 10 min. Spray the hot plate with alcoholic solution of sulfuric acid R. Heat again at 110 \u00b0C for 10 min. Allow to cool. Examine in daylight and in ultraviolet light at 365 nm.<\/p>\n

System suitability The chromatogram obtained with reference solution (b) shows 2 spots which may however not be completely separated.<\/p>\n

Results The principal spot in the chromatogram obtained with the test solution is similar in position, colour in daylight, fluorescence in ultraviolet light at 365 nm and size to the principal spot in the chromatogram obtained with reference solution (a).<\/p>\n

D. To about 1 mg add 0.5 mL of freshly prepared sulfomolybdic reagent R2. A blue colour develops which in ultraviolet light at 365 nm has an intense green fluorescence. Add 1 mL of sulfuric acid R and 9 mL of water<\/p>\n

R. The colour becomes pink with a yellowish fluorescence.<\/p>\n

E. Water (see Tests).<\/p>\n

TESTS<\/h2>\n

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

+ 76.0 to + 83.0 (anhydrous substance).<\/p>\n

Dissolve 0.250 g in ethanol (96 per cent) R and dilute to 25.0 mL with the same solvent.<\/p>\n

Related substances<\/h3>\n

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

Test solution: Dissolve 25 mg of the substance to be examined in 10 mL of acetonitrile R and dilute to 25.0 mL with methanol R2.<\/p>\n

Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with the mobile phase. Dilute 2.0 mL of this solution to 10.0 mL with the mobile phase.<\/p>\n

Reference solution (b): Mix equal volumes of a 1 mg\/mL solution of the substance to be examined in methanol R2 and of a 1 mg\/mL solution of 2,3-dichloro-5,6-dicyanobenzoquinone R in methanol R2. Allow to stand for 30 min before injection.<\/p>\n

Reference solution (c): Dissolve 5 mg of estradiol for peak identification CRS (containing impurities A, B and C) in 2 mL of acetonitrile R and dilute to 5.0 mL with methanol R2.<\/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

Mobile phase: To 400 mL of acetonitrile R add 50 mL of methanol R2 and 400 mL of water for chromatography R; allow to stand for 10 min, dilute to 1000 mL with water for chromatography R and mix again.<\/p>\n

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

Detection Spectrophotometer at 280 nm.<\/p>\n

Injection 20 \u03bcL.<\/p>\n

Run time: Twice the retention time of estradiol.<\/p>\n

Identification of impurities: Use the chromatogram supplied with estradiol for peak identification CRS and the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A, B and C; use the chromatogram obtained with reference solution (b) to identify the peak due to impurity D.<\/p>\n

Relative retention: With reference to estradiol (retention time = about 13 min): impurity D = about 0.9;
\nimpurity B = about 1.1; impurity A = about 1.4; impurity C = about 1.9.<\/p>\n

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

\u2014 resolution: minimum 2.5 between the peaks due to estradiol and impurity B.<\/p>\n

Limits:<\/p>\n

\u2014 correction factor: for the calculation of content, multiply the peak area of impurity D by 0.4;<\/p>\n

\u2014 impurities A, B, C, D: for each impurity, not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.3 per cent);<\/p>\n

\u2014 unspecified impurities: for each impurity, not more than 0.5 times the area of the principal peak in the
\nchromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\n

\u2014 total: not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent);
\n\u2014 disregard limit: 0.25 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n

Water (2.5.12)<\/h4>\n

2.9 per cent to 3.5 per cent, determined on 0.500 g.<\/p>\n

ASSAY<\/h2>\n

Dissolve 20.0 mg in ethanol (96 per cent) R and dilute to 100.0 mL with the same solvent. Dilute 5.0 mL of the solution to 50.0 mL with 0.1 M sodium hydroxide. Allow to cool to room temperature. Measure the absorbance (2.2.25) of the solution at the maximum at 238 nm.<\/p>\n

Calculate the content of C18<\/sub>H24<\/sub>O2<\/sub> taking the specific absorbance to be 335.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, B, C, D.<\/p>\n

\"Estradiol<\/p>\n

A. 3-hydroxyestra-1,3,5(10)-trien-17-one (estrone),<\/p>\n

\"Estradiol<\/p>\n

B. estra-1,3,5(10)-triene-3,17\u03b1-diol (17\u03b1-estradiol),<\/p>\n

\"Estradiol<\/p>\n

C. 4-methylestra-1,3,5(10)-triene-3,17\u03b2-diol,<\/p>\n

\"Estradiol<\/p>\n

D. estra-1,3,5(10),9(11)-tetraene-3,17\u03b2-diol.<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 0821) C18H24O2,1\u20442H2O\u00a0 \u00a0281.4 Action and use Estrogen. Preparations Estradiol Tablets Estradiol Transdermal Patches Estradiol and Norethisterone Tablets Estradiol and Norethisterone Acetate Tablets Estradiol Vaginal Tablets DEFINITION Estra-1,3,5(10)-triene-3,17\u03b2-diol hemihydrate. Content 97.0 per cent to 103.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, crystalline powder or colourless crystals. Solubility Practically insoluble…<\/p>\n","protected":false},"author":3,"featured_media":11124,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-11118","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\/11118","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=11118"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/11118\/revisions"}],"predecessor-version":[{"id":11126,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/11118\/revisions\/11126"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/11124"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=11118"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=11118"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=11118"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}