{"id":2460,"date":"2025-09-22T11:46:21","date_gmt":"2025-09-22T04:46:21","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=2460"},"modified":"2025-10-02T10:41:42","modified_gmt":"2025-10-02T03:41:42","slug":"atropine-sulfate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/atropine-sulfate\/","title":{"rendered":"Atropine Sulfate"},"content":{"rendered":"

(Ph. Eur. monograph 0068)<\/p>\n

C34<\/sub>H48<\/sub>N2<\/sub>O10<\/sub>S,H2<\/sub>O\u00a0 \u00a0 695\u00a0 \u00a0 5908-99-6<\/p>\n

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

Anticholinergic.<\/p>\n

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

Atropine Eye Drops<\/p>\n

Atropine Eye Ointment<\/p>\n

Atropine Injection<\/p>\n

Atropine Oral Solution<\/p>\n

Atropine Tablets<\/p>\n

DEFINITION<\/h2>\n

Bis[(1R,3r,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2RS)-3-hydroxy-2-phenylpropanoate] sulfate monohydrate.<\/p>\n

Content<\/h3>\n

99.0 per cent to 101.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Atropine Sulfate<\/p>\n

Solubility<\/h3>\n

Very soluble in water, freely soluble in ethanol (96 per cent).<\/p>\n

IDENTIFICATION<\/h2>\n

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

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

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

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

Comparison atropine sulfate CRS.<\/p>\n

C. Dissolve about 50 mg in 5 mL of water R and add 5 mL of picric acid solution R. The precipitate, washed with water R and dried at 100-105 \u00b0C for 2 h, melts (2.2.14) at 174 \u00b0C to 179 \u00b0C.<\/p>\n

D. To about 1 mg add 0.2 mL of fuming nitric acid R and evaporate to dryness in a water-bath. Dissolve the residue in 2 mL of acetone R and add 0.1 mL of a 30 g\/L solution of potassium hydroxide R in methanol R. A violet colour develops.<\/p>\n

E. It gives the reactions of sulfates (2.3.1).<\/p>\n

F. It gives the reaction of alkaloids (2.3.1).<\/p>\n

TESTS<\/h2>\n

pH (2.2.3)<\/h3>\n

4.5 to 6.2.<\/p>\n

Dissolve 0.6 g in carbon dioxide-free water R and dilute to 30 mL with the same solvent.<\/p>\n

Optical rotation (2.2.7)<\/h3>\n

-0.50\u00b0 to + 0.05\u00b0 (measured in a 2 dm tube).<\/p>\n

Dissolve 2.50 g in water 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 24 mg of the substance to be examined in mobile phase A and dilute to 100.0 mL with mobile phase A.<\/p>\n

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

Reference solution (b): Dissolve 5 mg of atropine impurity B CRS in the test solution and dilute to 20 mL with the test solution. Dilute 5 mL of this solution to 25 mL with mobile phase A.<\/p>\n

Reference solution (c): Dissolve the contents of a vial of atropine for peak identification CRS (containing impurities A, D, E, F, G and H) in 1 mL of mobile phase A.<\/p>\n

Reference solution (d): Dissolve 5 mg of tropic acid R (impurity C) in mobile phase A and dilute to 10 mL with mobile phase A. Dilute 1 mL of the solution to 100 mL with mobile phase A. Dilute 1 mL of this solution to 10 mL with mobile phase A.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.10 m, \u00d8 = 4.6 mm;<\/p>\n

\u2014 stationary phase: polar end-capped octadecylsilyl silica gel for chromatography R (3 \u03bcm).<\/p>\n

Mobile phase:<\/p>\n

\u2014 mobile phase A: dissolve 3.5 g of sodium dodecyl sulfate R in 606 mL of a 7.0 g\/L solution of potassium dihydrogen phosphate R previously adjusted to pH 3.3 with a 5.8 g\/L solution of phosphoric acid R, and mix with 320 mL of acetonitrile R1;<\/p>\n

\u2014 mobile phase B: acetonitrile R1;<\/p>\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 – 2<\/td>\n95<\/td>\n5<\/td>\n<\/tr>\n
2 – 20<\/td>\n\u00a095 \u2192 70<\/td>\n\u00a05 \u2192 30<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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

Detection: Spectrophotometer at 210 nm.<\/p>\n

Injection: 10 \u03bcL.<\/p>\n

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

Relative retention: With reference to atropine (retention time = about 11 min): impurity C = about 0.2;
\nimpurity E = about 0.67; impurity D = about 0.73; impurity F = about 0.8; impurity B = about 0.89; impurity H = about 0.93; impurity G = about 1.1; impurity A = about 1.7.<\/p>\n

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

\u2014 resolution: minimum 2.5 between the peaks due to impurity B and atropine.<\/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 A = 0.6; impurity C = 0.6;<\/p>\n

\u2014 impurities E, H: for each impurity, 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 impurities A, B, C, D, F, G: for each impurity, not more than twice the area of the principal peak in the
\nchromatogram obtained with reference solution (a) (0.2 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 5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 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

Water (2.5.12)<\/h4>\n

2.0 per cent to 4.0 per cent, determined on 0.500 g.<\/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 0.500 g in 30 mL of anhydrous acetic acid R, warming if necessary. Cool the solution. 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 67.68 mg of C34H48N2O10S.<\/p>\n

STORAGE<\/h2>\n

Protected from light.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, B, C, D, E, F, G, H.<\/p>\n

\"Atropine<\/p>\n

A. (1R,3r,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl 2-phenylpropenoate (apoatropine),<\/p>\n

\"Atropine<\/p>\n

B. (1R,3r,5S)-8-azabicyclo[3.2.1]oct-3-yl (2RS)-3-hydroxy-2-phenylpropanoate (noratropine),<\/p>\n

\"Atropine<\/p>\n

C. (2RS)-3-hydroxy-2-phenylpropanoic acid (tropic acid),<\/p>\n

D. (1R,3S,5R,6RS)-6-hydroxy-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2S)-3-hydroxy-2-phenylpropanoate (6-
\nhydroxyhyoscyamine),<\/p>\n

\"Atropine<\/p>\n

E. (1S,3R,5S,6RS)-6-hydroxy-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2S)-3-hydroxy-2-phenylpropanoate (7-
\nhydroxyhyoscyamine),<\/p>\n

\"Atropine<\/p>\n

F. (1R,2R,4S,5S,7s)-9-methyl-3-oxa-9-azatricyclo[3.3.1.0 ]non-7-yl (2S)-3-hydroxy-2-phenylpropanoate (hyoscine),<\/p>\n

\"Atropine<\/p>\n

G. (1R,3r,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2RS)-2-hydroxy-3-phenylpropanoate (littorine),<\/p>\n

H. unknown structure.<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 0068) C34H48N2O10S,H2O\u00a0 \u00a0 695\u00a0 \u00a0 5908-99-6 Action and use Anticholinergic. Preparations Atropine Eye Drops Atropine Eye Ointment Atropine Injection Atropine Oral Solution Atropine Tablets DEFINITION Bis[(1R,3r,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2RS)-3-hydroxy-2-phenylpropanoate] sulfate monohydrate. Content 99.0 per cent to 101.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, crystalline powder or colourless crystals. Atropine Sulfate…<\/p>\n","protected":false},"author":3,"featured_media":2480,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-2460","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\/2460","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=2460"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/2460\/revisions"}],"predecessor-version":[{"id":7575,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/2460\/revisions\/7575"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/2480"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=2460"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=2460"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=2460"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}