{"id":24914,"date":"2025-11-03T16:55:33","date_gmt":"2025-11-03T09:55:33","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=24914"},"modified":"2025-11-03T17:10:29","modified_gmt":"2025-11-03T10:10:29","slug":"methadone-hydrochloride","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/methadone-hydrochloride\/","title":{"rendered":"Methadone Hydrochloride"},"content":{"rendered":"

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

$\"Methadone$ <\/p>\n

C_{21<\/sub>H_{28<\/sub>ClNO 345.9 1095-90-5<\/p>\n}}

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

Opioid receptor agonist; analgesic; treatment of opioid dependence.<\/p>\n

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

Methadone Concentrate for Oral Solution
\nMethadone Injection
\nMethadone Oral Solution (1 mg per ml)
\nMethadone Tablets<\/p>\n

DEFINITION<\/h2>\n
(6RS)-6-(Dimethylamino)-4,4-diphenylheptan-3-one hydrochloride.<\/p>\n
Content<\/strong><\/p>\n
99.0 per cent to 101.0 per cent (dried substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/strong><\/p>\n
White or almost white, crystalline powder.<\/p>\n
Solubility<\/strong><\/p>\n
Soluble in water, freely soluble in ethanol (96 per cent).<\/p>\n
IDENTIFICATION<\/h2>\n
First identification: A, C, D.<\/p>\n
Second identification: A, B, D.<\/p>\n
A. Optical rotation (see Tests).
\nB. Melting point (2.2.14): 233 \u00b0C to 236 \u00b0C.
\nC. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison Ph. Eur. reference spectrum of methadone hydrochloride.<\/p>\n
D. Dilute 1 mL of solution S (see Tests) to 5 mL with water R and add 1 mL of dilute ammonia R1. Mix, allow to stand for 5 min and filter. The filtrate gives reaction (a) of chlorides (2.3.1).<\/p>\n
TESTS<\/h2>\n
Solution S<\/strong><\/p>\n
Dissolve 2.50 g in carbon dioxide-free water R and dilute to 50.0 mL with the same solvent.<\/p>\n
Appearance of solution<\/strong><\/p>\n
Solution S is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n
Acidity or alkalinity<\/strong><\/p>\n
Dilute 10 mL of solution S to 25 mL with carbon dioxide-free water R. To 10 mL of the solution add 0.2 mL of methyl red solution R and 0.2 mL of 0.01 M sodium hydroxide. The solution is yellow. Add 0.4 mL of 0.01 M hydrochloric acid. The solution is red.<\/p>\n
Optical rotation (2.2.7)<\/strong><\/p>\n
-0.05\u00b0 to + 0.05\u00b0, determined on solution S in a 2 dm tube.<\/p>\n
Related substances<\/strong><\/p>\n
Gas chromatography (2.2.28).
\nTest solution Dissolve 0.100 g of the substance to be examined in methanol R and dilute to 10.0 mL with the same solvent.<\/p>\n
Reference solution (a) Dilute 1.0 mL of the test solution to 10.0 mL with methanol R. Dilute 1.0 mL of this solution to 100.0 mL with methanol R.
\nReference solution (b) Dissolve 5 mg of imipramine hydrochloride CRS and 5 mg of cyclobenzaprine hydrochloride CRS in 100.0 mL of methanol R.<\/p>\n
Column:
\n\u2014 material: fused silica;
\n\u2014 size: l = 50 m, \u00d8 = 0.32 mm;
\n\u2014 stationary phase: phenyl(5)methyl(95)polysiloxane R (film thickness 1.05 \u03bcm).<\/p>\n
Carrier gas helium for chromatography R.<\/p>\n
Flow rate 1.2 mL\/min.<\/p>\n
Injection liner Packed with deactivated glass wool to wipe the needle.<\/p>\n
Split ratio 1:100.<\/p>\n
Temperature:<\/p>\n\n\n\n\n\n\n\n
<\/td>\n Time
\n(min)<\/td>\n Temperature
\n(\u00b0C)<\/td>\n<\/tr>\n
Column<\/td>\n 0 – 4<\/td>\n 150 \u2192 250<\/td>\n<\/tr>\n
<\/td>\n 4 – 35<\/td>\n 250<\/td>\n<\/tr>\n
Injection<\/td>\n <\/td>\n 200<\/td>\n<\/tr>\n
Detector<\/td>\n <\/td>\n 250<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Detection Flame ionisation.<\/p>\n
Injection 2 \u03bcL.<\/p>\n
Run time 1.5 times the retention time of methadone.<\/p>\n
Relative retention With reference to methadone (retention time = about 25 min): impurity E = about 0.44; impurity C = about 0.81; impurity B = about 0.89; impurity D = about 0.98; impurity A = about 1.14; imipramine = about 1.19; cyclobenzaprine = about 1.24.<\/p>\n
System suitability Reference solution (b):
\n\u2014 resolution: minimum 3.0 between the peaks due to imipramine and cyclobenzaprine.<\/p>\n
Limits:
\n\u2014 impurities A, B, C, D, E: for each impurity, not more than the area of the principal peak in the
\nchromatogram obtained with reference solution (a) (0.1 per cent);
\n\u2014 unspecified impurities: for each impurity, not more than the area of the principal peak in the
\nchromatogram obtained with reference solution (a) (0.10 per cent);
\n\u2014 total: not more than 3 times the area of the principal peak in the chromatogram obtained with
\nreference solution (a) (0.3 per cent);
\n\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference
\nsolution (a) (0.05 per cent).<\/p>\n
Loss on drying (2.2.32)<\/strong><\/p>\n
Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C.<\/p>\n
Sulfated ash (2.4.14)<\/strong><\/p>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.300 g in a mixture of 5 mL of 0.01 M hydrochloric acid and 50 mL of anhydrous ethanol R. Carry out a potentiometric titration (2.2.20), using 0.1 M sodium hydroxide. Read the volume added between the 2 points of inflexion. Carry out a blank titration.<\/p>\n
1 mL of 0.1 M sodium hydroxide is equivalent to 34.59 mg of C_{21<\/sub>H_{28<\/sub>ClNO.<\/p>\n}}
STORAGE<\/h2>\n
Protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities A, B, C, D, E.<\/em><\/p>\n
$\"(2RS)-4-imino-N,N,2-trimethyl-3,3-diphenylhexan-1-amine$ <\/p>\n
A. (2RS)-4-imino-N,N,2-trimethyl-3,3-diphenylhexan-1-amine (isomethadone ketimine),<\/p>\n
$\"(4RS)-4-(dimethylamino)-2,2-diphenylpentanenitrile$ <\/p>\n
B. (4RS)-4-(dimethylamino)-2,2-diphenylpentanenitrile (didiavalo),<\/p>\n
$\"(3RS)-4-(dimethylamino)-3-methyl-2,2-diphenylbutanenitrile$ <\/p>\n
C. (3RS)-4-(dimethylamino)-3-methyl-2,2-diphenylbutanenitrile (isodidiavalo),<\/p>\n
$\"(5RS)-6-(dimethylamino)-5-methyl-4,4-diphenylhexan-3-one$ <\/p>\n
D. (5RS)-6-(dimethylamino)-5-methyl-4,4-diphenylhexan-3-one (isomethadone),<\/p>\n
$\"diphenylacetonitrile\"$ <\/p>\n
E. diphenylacetonitrile.<\/p>\n","protected":false},"excerpt":{"rendered":"
BP 2025 (Ph. Eur. 11.6 update) C21H28ClNO 345.9 1095-90-5 Action and use Opioid receptor agonist; analgesic; treatment of opioid dependence. Preparations Methadone Concentrate for Oral Solution Methadone Injection Methadone Oral Solution (1 mg per ml) Methadone Tablets DEFINITION (6RS)-6-(Dimethylamino)-4,4-diphenylheptan-3-one hydrochloride. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost…<\/p>\n","protected":false},"author":5,"featured_media":24955,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-24914","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\/24914","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=24914"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/24914\/revisions"}],"predecessor-version":[{"id":25022,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/24914\/revisions\/25022"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/24955"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=24914"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=24914"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=24914"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

<\/td>\n	Time \n(min)<\/td>\n	Temperature \n(\u00b0C)<\/td>\n<\/tr>\n
Column<\/td>\n	0 – 4<\/td>\n	150 \u2192 250<\/td>\n<\/tr>\n
<\/td>\n	4 – 35<\/td>\n	250<\/td>\n<\/tr>\n
Injection<\/td>\n	<\/td>\n	200<\/td>\n<\/tr>\n
Detector<\/td>\n	<\/td>\n	250<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Detection Flame ionisation.<\/p>\n Injection 2 \u03bcL.<\/p>\n Run time 1.5 times the retention time of methadone.<\/p>\n Relative retention With reference to methadone (retention time = about 25 min): impurity E = about 0.44; impurity C = about 0.81; impurity B = about 0.89; impurity D = about 0.98; impurity A = about 1.14; imipramine = about 1.19; cyclobenzaprine = about 1.24.<\/p>\n System suitability Reference solution (b): \n\u2014 resolution: minimum 3.0 between the peaks due to imipramine and cyclobenzaprine.<\/p>\n Limits: \n\u2014 impurities A, B, C, D, E: for each impurity, not more than the area of the principal peak in the \nchromatogram obtained with reference solution (a) (0.1 per cent); \n\u2014 unspecified impurities: for each impurity, not more than the area of the principal peak in the \nchromatogram obtained with reference solution (a) (0.10 per cent); \n\u2014 total: not more than 3 times the area of the principal peak in the chromatogram obtained with \nreference solution (a) (0.3 per cent); \n\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference \nsolution (a) (0.05 per cent).<\/p>\n Loss on drying (2.2.32)<\/strong><\/p>\n Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C.<\/p>\n Sulfated ash (2.4.14)<\/strong><\/p>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n ASSAY<\/h2>\n Dissolve 0.300 g in a mixture of 5 mL of 0.01 M hydrochloric acid and 50 mL of anhydrous ethanol R. Carry out a potentiometric titration (2.2.20), using 0.1 M sodium hydroxide. Read the volume added between the 2 points of inflexion. Carry out a blank titration.<\/p>\n 1 mL of 0.1 M sodium hydroxide is equivalent to 34.59 mg of C_{21<\/sub>H_{28<\/sub>ClNO.<\/p>\n}} STORAGE<\/h2>\n Protected from light.<\/p>\n IMPURITIES<\/h2>\n Specified impurities A, B, C, D, E.<\/em><\/p>\n $\"(2RS)-4-imino-N,N,2-trimethyl-3,3-diphenylhexan-1-amine$ <\/p>\n A. (2RS)-4-imino-N,N,2-trimethyl-3,3-diphenylhexan-1-amine (isomethadone ketimine),<\/p>\n $\"(4RS)-4-(dimethylamino)-2,2-diphenylpentanenitrile$ <\/p>\n B. (4RS)-4-(dimethylamino)-2,2-diphenylpentanenitrile (didiavalo),<\/p>\n $\"(3RS)-4-(dimethylamino)-3-methyl-2,2-diphenylbutanenitrile$ <\/p>\n C. (3RS)-4-(dimethylamino)-3-methyl-2,2-diphenylbutanenitrile (isodidiavalo),<\/p>\n $\"(5RS)-6-(dimethylamino)-5-methyl-4,4-diphenylhexan-3-one$ <\/p>\n D. (5RS)-6-(dimethylamino)-5-methyl-4,4-diphenylhexan-3-one (isomethadone),<\/p>\n $\"diphenylacetonitrile\"$ <\/p>\n E. diphenylacetonitrile.<\/p>\n","protected":false},"excerpt":{"rendered":" BP 2025 (Ph. Eur. 11.6 update) C21H28ClNO 345.9 1095-90-5 Action and use Opioid receptor agonist; analgesic; treatment of opioid dependence. Preparations Methadone Concentrate for Oral Solution Methadone Injection Methadone Oral Solution (1 mg per ml) Methadone Tablets DEFINITION (6RS)-6-(Dimethylamino)-4,4-diphenylheptan-3-one hydrochloride. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost…<\/p>\n","protected":false},"author":5,"featured_media":24955,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-24914","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\/24914","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=24914"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/24914\/revisions"}],"predecessor-version":[{"id":25022,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/24914\/revisions\/25022"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/24955"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=24914"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=24914"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=24914"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

STORAGE<\/h2>\nProtected from light.<\/p>\n

STORAGE<\/h2>\n
Protected from light.<\/p>\n