{"id":25691,"date":"2025-11-04T16:33:17","date_gmt":"2025-11-04T09:33:17","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=25691"},"modified":"2025-11-04T16:33:17","modified_gmt":"2025-11-04T09:33:17","slug":"naloxone-hydrochloride","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/naloxone-hydrochloride\/","title":{"rendered":"Naloxone Hydrochloride"},"content":{"rendered":"

Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n

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

Opioid receptor antagonist.<\/p>\n

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

Naloxone Injection<\/p>\n

Ph Eur<\/p>\n

\n
DEFINITION<\/h2>\n
4,5\u03b1-Epoxy-3,14-dihydroxy-17-(prop-2-enyl)morphinan-6-one hydrochloride dihydrate.<\/p>\n
Content<\/strong><\/p>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white, hygroscopic, crystalline powder.<\/p>\n
Solubility<\/h3>\n
Freely soluble in water, soluble in ethanol (96 per cent), practically insoluble in toluene.<\/p>\n
IDENTIFICATION<\/h2>\n
First identification: A, C.<\/em><\/p>\n
Second identification: B, C.<\/em><\/p>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison\u00a0 naloxone hydrochloride dihydrate CRS.<\/em><\/p>\n
B. Thin-layer chromatography (2.2.27).<\/p>\n
Test solution<\/em>\u00a0 Dissolve 8 mg of the substance to be examined in 0.5 mL of water R and dilute to 1 mL with methanol R.<\/p>\n
Reference solution<\/em>\u00a0 Dissolve 8 mg of naloxone hydrochloride dihydrate CRS in 0.5 mL of water R and dilute to 1 mL with methanol R.<\/p>\n
Plate\u00a0 TLC<\/em> silica gel G plate R.<\/p>\n
Mobile phase\u00a0<\/em> Mix 5 volumes of methanol R and 95 volumes of the upper layer from a mixture of 60 mL of dilute ammonia R2 and 100 mL of butanol R. Application 5 \u00b5L.<\/p>\n
Development\u00a0<\/em> Over 2\/3 of the plate.<\/p>\n
Drying<\/em>\u00a0 In air.<\/p>\n
Detection\u00a0<\/em> Spray with a freshly prepared 5 g\/L solution of potassium ferricyanide R in ferric chloride solution R1; examine in daylight.<\/p>\n
Results\u00a0<\/em> The principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with the reference solution.<\/p>\n
C. It gives reaction (a) of chlorides (2.3.1).<\/p>\n
TESTS<\/h2>\n
Solution S<\/h3>\n
Dissolve 0.50 g in carbon dioxide-free water R and dilute to 25.0 mL with the same solvent.<\/p>\n
Appearance of solution<\/h3>\n
Solution S is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n
Acidity or alkalinity<\/h3>\n
To 10.0 mL of solution S add 0.05 mL of methyl red solution R. Not more than 0.2 mL of 0.02 M sodium hydroxide or 0.02 M hydrochloric acid is required to change the colour of the indicator.<\/p>\n
Specific optical rotation (2.2.7)<\/strong><\/p>\n
-181 to -170 (anhydrous substance), determined on solution S.<\/p>\n
Impurity D<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Solution A<\/em>\u00a0 Dissolve 1.58 g of ammonium hydrogen carbonate R in 950 mL of water for chromatography R, adjust to pH 9.0 with concentrated ammonia R and dilute to 1000 mL with water for chromatography R.<\/p>\n
Test solution<\/em>\u00a0 Dissolve 0.500 g of the substance to be examined in a 10.3 g\/L solution of hydrochloric acid R
\nand dilute to 20.0 mL with the same solution.<\/p>\n
Reference solution (a)\u00a0<\/em> Dissolve 10.0 mg of naloxone impurity D CRS in a 10.3 g\/L solution of hydrochloric acid R and dilute to 20.0 mL with the same solution. Dilute 5.0 mL of this solution to 100.0 mL with a 10.3 g\/L solution of hydrochloric acid R.<\/p>\n
Reference solution (b)<\/em>\u00a0 Dilute 5.0 mL of reference solution (a) to 100.0 mL with a 10.3 g\/L solution of
\nhydrochloric acid R.<\/p>\n
Reference solution (c)<\/em>\u00a0 To 4.0 mL of the test solution add 2.0 mL of reference solution (a) and dilute to
\n20.0 mL with a 10.3 g\/L solution of hydrochloric acid R. 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 \u00b5m);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase:<\/em><\/p>\n
\u2014 mobile phase A: acetonitrile R1, solution A (20:80 V\/V);<\/p>\n
\u2014 mobile phase B: acetonitrile R1, solution A (40:60 V\/V);<\/p>\n\n\n\n\n\n\n
Time (min)<\/strong><\/td>\n Mobile phase A (per cent V\/V)<\/strong><\/td>\n Mobile phase B (per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 50<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
50 – 51<\/td>\n 100 \u2192 0<\/td>\n 0 \u2192 100<\/td>\n<\/tr>\n
51 – 60<\/td>\n 0<\/td>\n 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate\u00a0 2.0 mL\/min.<\/p>\n
Detection<\/em>\u00a0 Spectrophotometer at 210 nm.<\/p>\n
Injection\u00a0<\/em> 10 \u00b5L of the test solution and reference solutions (b) and (c).<\/p>\n
Relative retention\u00a0<\/em> With reference to naloxone (retention time = about 50 min): impurity D = about 0.8.<\/p>\n
System suitability\u00a0<\/em> Reference solution (c):<\/p>\n
\u2014 symmetry factor:<\/em> maximum 1.8 for the peak due to impurity D.<\/p>\n
Limit:<\/em><\/p>\n
\u2014 impurity D: not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (75 ppm).<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Solution A\u00a0<\/em> Dissolve 1.10 g of sodium octanesulfonate R in 950 mL of water for chromatography R, adjust to pH 2.0 with a 50 per cent V\/V solution of phosphoric acid R, filter and dilute to 1000 mL with water for chromatography R.<\/p>\n
Test solution<\/em>\u00a0 Dissolve 0.125 g of the substance to be examined in a 10.3 g\/L solution of hydrochloric acid R
\nand dilute to 25.0 mL with the same solution.<\/p>\n
Reference solution (a)\u00a0<\/em> Dissolve the contents of a vial of naloxone for peak identification CRS (containing impurities A, B, C, D, E and F) in 1 mL of a 10.3 g\/L solution of hydrochloric acid R.<\/p>\n
Reference solution (b)\u00a0<\/em> Dilute 1.0 mL of the test solution to 20.0 mL with a 10.3 g\/L solution of hydrochloric acid R. Dilute 1.0 mL of this solution to 25.0 mL with a 10.3 g\/L solution of hydrochloric acid R.<\/p>\n
Column:<\/em><\/p>\n
\u2014 size: l = 0.125 m, \u00d8 = 4.0 mm;<\/p>\n
\u2014 stationary phase: end-capped octylsilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase:<\/em><\/p>\n
\u2014 mobile phase A: acetonitrile R, tetrahydrofuran R, solution A (2:4:94 V\/V\/V);<\/p>\n
\u2014 mobile phase B: tetrahydrofuran R, acetonitrile R, solution A (4:17:79 V\/V\/V);<\/p>\n\n\n\n\n\n
Time (min)<\/strong><\/td>\n Mobile phase A (per cent V\/V)<\/strong><\/td>\n Mobile phase B (per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 40<\/td>\n 100 \u2192 0<\/td>\n 0 \u2192 100<\/td>\n<\/tr>\n
40 – 50<\/td>\n 0<\/td>\n 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate\u00a0<\/em> 1.5 mL\/min.<\/p>\n
Detection\u00a0<\/em> Spectrophotometer at 230 nm.<\/p>\n
Injection\u00a0<\/em> 20 \u00b5L.<\/p>\n
Relative retention\u00a0<\/em> With reference to naloxone (retention time = about 11 min): impurity C = about 0.6; impurity A = about 0.8; impurity F = about 0.9; impurity D = about 1.1; impurity E = about 3.0; impurity B = about 3.2.<\/p>\n
Identification of impurities\u00a0<\/em> Use the chomatogram supplied with naloxone for peak identification CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities A, B, C, D, E and F.<\/p>\n
System suitability<\/em>\u00a0 Reference solution (a):<\/p>\n
\u2014 peak-to-valley ratio:<\/em> minimum 2.0, where Hp = height above the baseline of the peak due to impurity D and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to naloxone.<\/p>\n
Limits:<\/em><\/p>\n
\u2014 correction factor: for the calculation of content, multiply the peak area of impurity E by 0.5;<\/p>\n
\u2014 impurities A, B, C, E, F: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent);<\/p>\n
\u2014 unspecified impurities: for each impurity, not more than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.10 per cent);<\/p>\n
\u2014 total: not more than 4 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.8 per cent);<\/p>\n
\u2014 disregard limit: 0.25 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n
Water (2.5.12)<\/strong><\/p>\n
7.5 per cent to 11.0 per cent, determined on 0.200 g.<\/p>\n
Sulfated ash (2.4.14)<\/strong><\/p>\n
Maximum 0.2 per cent, determined on 0.50 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.300 g in 50 mL of ethanol (96 per cent) R and add 5.0 mL of 0.01 M hydrochloric acid. Carry out a potentiometric titration (2.2.20), using 0.1 M ethanolic sodium hydroxide. Read the volume added between the 2 points of inflexion.<\/p>\n
1 mL of 0.1 M ethanolic sodium hydroxide is equivalent to 36.38 mg of C_{19<\/sub>H_{22<\/sub>ClNO_{4<\/sub>.<\/p>\n}}}
STORAGE<\/h2>\n
In an airtight container, protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities\u00a0 A, B, C, D, E, F.<\/em><\/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.<\/em><\/p>\n
Control of impurities in substances for pharmaceutical use)\u00a0 G.<\/em><\/p>\n
A. 4,5\u03b1-epoxy-3,14-dihydroxymorphinan-6-one (noroxymorphone),<\/p>\n
B. 4,5\u03b1-epoxy-14-hydroxy-17-(prop-2-enyl)-3-(prop-2-enyloxy)morphinan-6-one (3-O-allylnaloxone),<\/p>\n
C. 4,5\u03b1-epoxy-3,10\u03b1,14-trihydroxy-17-(prop-2-enyl)morphinan-6-one (10\u03b1-hydroxynaloxone),<\/p>\n
D. 7,8-didehydro-4,5\u03b1-epoxy-3,14-dihydroxy-17-(prop-2-enyl)morphinan-6-one (7,8-didehydronaloxone),<\/p>\n
E. 4,5\u03b1:4\u2032,5\u2032\u03b1-diepoxy-3,3\u2032,14,14\u2032-tetrahydroxy-17,17\u2032-bis(prop-2-enyl)-2,2\u2032-bimorphinanyl-6,6\u2032-dione (2,2\u2032- binaloxone),<\/p>\n
F. 4,5\u03b1-epoxy-3,10\u03b2,14-trihydroxy-17-(prop-2-enyl)morphinan-6-one (10\u03b2-hydroxynaloxone),<\/p>\n
G. 4,5\u03b1-epoxy-14-hydroxy-3-methoxy-17-(prop-2-enyl)morphinan-6-one (3-O-methylnaloxone).<\/p>\n
\n
Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":"
Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Opioid receptor antagonist. Preparation Naloxone Injection Ph Eur DEFINITION 4,5\u03b1-Epoxy-3,14-dihydroxy-17-(prop-2-enyl)morphinan-6-one hydrochloride dihydrate. Content 98.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, hygroscopic, crystalline powder. Solubility Freely soluble in water, soluble in ethanol (96 per cent), practically insoluble in…<\/p>\n","protected":false},"author":5,"featured_media":25692,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25691","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\/25691","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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=25691"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25691\/revisions"}],"predecessor-version":[{"id":25714,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25691\/revisions\/25714"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25692"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25691"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25691"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25691"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

DEFINITION<\/h2>\n4,5\u03b1-Epoxy-3,14-dihydroxy-17-(prop-2-enyl)morphinan-6-one hydrochloride dihydrate.<\/p>\nContent<\/strong><\/p>\n98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

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

Solubility<\/h3>\nFreely soluble in water, soluble in ethanol (96 per cent), practically insoluble in toluene.<\/p>\n

Solution S<\/h3>\nDissolve 0.50 g in carbon dioxide-free water R and dilute to 25.0 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\nSolution S is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n

STORAGE<\/h2>\nIn an airtight container, protected from light.<\/p>\n

DEFINITION<\/h2>\n
4,5\u03b1-Epoxy-3,14-dihydroxy-17-(prop-2-enyl)morphinan-6-one hydrochloride dihydrate.<\/p>\n
Content<\/strong><\/p>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

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

Solubility<\/h3>\n
Freely soluble in water, soluble in ethanol (96 per cent), practically insoluble in toluene.<\/p>\n

Solution S<\/h3>\n
Dissolve 0.50 g in carbon dioxide-free water R and dilute to 25.0 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n
Solution S is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n

STORAGE<\/h2>\n
In an airtight container, protected from light.<\/p>\n