{"id":1182,"date":"2025-09-18T10:36:21","date_gmt":"2025-09-18T03:36:21","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=1182"},"modified":"2025-11-15T10:56:36","modified_gmt":"2025-11-15T03:56:36","slug":"acetylcysteine","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/acetylcysteine\/","title":{"rendered":"Acetylcysteine"},"content":{"rendered":"

(Ph. Eur. monograph 0967)<\/p>\n

C5<\/sub>H9<\/sub>NO3<\/sub>S\u00a0 \u00a0 \u00a0 163.2\u00a0 \u00a0 \u00a0 616-91-1<\/p>\n

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

Sulfydryl donor; antidote to paracetamol poisoning; mucolytic.<\/p>\n

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

Acetylcysteine Eye Drops<\/p>\n

Acetylcysteine Injection<\/p>\n

DEFINITION<\/h2>\n

(2R)-2-Acetamido-3-sulfanylpropanoic acid.<\/p>\n

Content<\/h3>\n

98.5 per cent to 101.0 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Solubility<\/h3>\n

Freely soluble in water and in ethanol (96 per cent), practically insoluble in methylene chloride.<\/p>\n

IDENTIFICATION<\/h2>\n

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

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

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

B. Melting point (2.2.14).<\/p>\n

Determination A: Determine the melting point of the substance to be examined.<\/p>\n

Result A: 108 \u00b0C to 110 \u00b0C.<\/p>\n

Determination B: Mix equal parts of the substance to be examined and acetylcysteine CRS and determine the melting point of the mixture.<\/p>\n

Result B: The absolute difference between the melting point of the mixture and the value obtained in determination A is not greater than 2 \u00b0C.<\/p>\n

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

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

TESTS<\/h2>\n

Appearance of solution<\/h3>\n

The solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n

Dissolve 0.5 g in water R and dilute to 10 mL with the same solvent.<\/p>\n

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

+ 21.0 to + 27.0 (dried substance).<\/p>\n

Mix 1.25 g and 1 mL of a 10 g\/L solution of sodium edetate R. Add 7.5 mL of a 40 g\/L solution of sodium hydroxide R, mix and dissolve. Dilute to 25.0 mL with phosphate buffer solution pH 7.0 R2.<\/p>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n

Solution A: 1.03 g\/L solution of hydrochloric acid R.<\/p>\n

Test solution: Suspend 0.120 g of the substance to be examined in solution A and dilute to 15.0 mL with solution A, ensuring complete dissolution.<\/p>\n

Reference solution (a): Dilute 5.0 mL of the test solution to 50.0 mL with solution A. Dilute 1.0 mL of this solution to 100.0 mL with solution A.<\/p>\n

Reference solution (b): Dissolve 4 mg of L-cystine R (impurity A) in solution A and dilute to 10 mL with solution A.<\/p>\n

Reference solution (c): Dissolve 3 mg of L-cysteine R (impurity B), 5 mg of acetylcysteine impurity C CRS and 2.5 mg of acetylcysteine impurity D CRS in solution A, mix with 4 mL of reference solution (b) and dilute to 20 mL with solution A. Dilute 1 mL of this solution to 10 mL with the test solution.<\/p>\n

Reference solution (d): Dissolve 2 mg of sodium 2-methyl-2-thiazoline-4-carboxylate R in solution A and dilute to 50 mL with solution A.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25 m, \u00d8 = 4.0 mm;<\/p>\n

\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 \u03bcm).<\/p>\n

Mobile phase acetonitrile for chromatography R, water for chromatography R previously adjusted to pH 3.0 with phosphoric acid R (3:97 V\/V).<\/p>\n

Flow rate: 1.0 mL\/min.<\/p>\n

Detection: Spectrophotometer at 220 nm.<\/p>\n

Injection: 20 \u03bcL of the test solution and reference solutions (a), (c) and (d).<\/p>\n

Run time: 3 times the retention time of acetylcysteine.<\/p>\n

Identification of impurities: Use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A, B, C and D; use the chromatogram obtained with reference solution (d) to identify the peak due to 2-methyl-2- thiazoline-4-carboxylic acid.<\/p>\n

Relative retention: With reference to acetylcysteine (retention time = about 5 min): impurity A = about 0.48; impurity B = about 0.53; 2-methyl-2-thiazoline-4-carboxylic acid = about 0.8; impurity C = about 2.1; impurity D = about 2.6.<\/p>\n

System suitability:<\/p>\n

\u2014 resolution: minimum 1.5 between the peaks due to impurities A and B in the chromatogram obtained with reference solution (c);<\/p>\n

\u2014 peak-to-valley ratio: minimum 5.0, where Hp = height above the baseline of the peak due to 2-methyl-2-thiazoline-4- carboxylic acid and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to acetylcysteine in the chromatogram obtained with reference solution (c);<\/p>\n

\u2014 symmetry factor: maximum 2.2 for the peak due to acetylcysteine in the chromatogram obtained with reference solution (a).<\/p>\n

Calculation of percentage contents:<\/p>\n

\u2014 correction factors: multiply the peak areas of the following impurities by the corresponding correction factor: impurity B = 3.4; impurity C = 0.7; impurity D = 0.3;<\/p>\n

\u2014 for each impurity, use the concentration of acetylcysteine in reference solution (a).<\/p>\n

Limits:<\/p>\n

\u2014 impurity C: maximum 0.3 per cent;<\/p>\n

\u2014 impurity B: maximum 0.2 per cent;<\/p>\n

\u2014 impurity D: maximum 0.15 per cent;<\/p>\n

\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n

\u2014 total: maximum 0.5 per cent;<\/p>\n

\u2014 reporting threshold: 0.05 per cent; disregard the peak due to 2-methyl-2-thiazoline-4-carboxylic acid, which is formed due to in situ degradation of acetylcysteine in acidic solutions such as solution A.<\/p>\n

The thresholds indicated under Related substances (Table 2034.-1) in the general monograph Substances for pharmaceutical use (2034) do not apply.<\/p>\n

Zinc<\/h4>\n

Maximum 10 ppm.<\/p>\n

Atomic absorption spectrometry (2.2.23, Method II).<\/p>\n

Test solution: Dissolve 1.00 g in a 0.103 g\/L solution of hydrochloric acid R and dilute to 50.0 mL with the same solution.<\/p>\n

Reference solutions: Prepare the reference solutions using zinc standard solution (5 mg\/mL Zn) R, diluting with a 0.103 g\/L solution of hydrochloric acid R.<\/p>\n

Source: Zinc hollow-cathode lamp.<\/p>\n

Wavelength: 213.9 nm.<\/p>\n

Atomisation device: Air-acetylene flame.<\/p>\n

Use a correction procedure for non-specific absorption.<\/p>\n

Loss on drying (2.2.32)<\/h4>\n

Maximum 1.0 per cent, determined on 1.000 g by drying in vacuo at 70 \u00b0C for 3 h.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n

Maximum 0.2 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n

Dissolve 0.140 g in 60 mL of water R and add 10 mL of dilute hydrochloric acid R. Add 10 mL of potassium iodide solution R and titrate with 0.05 M iodine, determining the end-point potentiometrically (2.2.20).<\/p>\n

1 mL of 0.05 M iodine is equivalent to 16.32 mg of C5H9NO3S.<\/p>\n

STORAGE<\/h2>\n

Protected from light.<\/p>\n

IMPURITIES<\/h2>\n

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

\"Acetylcysteine\"<\/p>\n

A. 3,3\u2032-disulfanediylbis[(2R)-2-aminopropanoic acid] (L-cystine),<\/p>\n

\"Acetylcysteine\"<\/p>\n

B. (2R)-2-amino-3-sulfanylpropanoic acid (L-cysteine),<\/p>\n

\"Acetylcysteine\"<\/p>\n

C. 3,3\u2032-disulfanediylbis[(2R)-2-acetamidopropanoic acid] (N,N\u2032-diacetyl-L-cystine),<\/p>\n

\"Acetylcysteine\"<\/p>\n

D. (2R)-2-acetamido-3-(acetylsulfanyl)propanoic acid (N,S-diacetyl-L-cysteine).<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 0967) C5H9NO3S\u00a0 \u00a0 \u00a0 163.2\u00a0 \u00a0 \u00a0 616-91-1 Action and use Sulfydryl donor; antidote to paracetamol poisoning; mucolytic. Preparations Acetylcysteine Eye Drops Acetylcysteine Injection DEFINITION (2R)-2-Acetamido-3-sulfanylpropanoic acid. Content 98.5 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder or colourless crystals. Solubility Freely soluble in…<\/p>\n","protected":false},"author":2,"featured_media":1192,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-1182","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\/1182","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=1182"}],"version-history":[{"count":6,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1182\/revisions"}],"predecessor-version":[{"id":6822,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1182\/revisions\/6822"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/1192"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=1182"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=1182"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=1182"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}