{"id":1395,"date":"2025-09-19T08:59:18","date_gmt":"2025-09-19T01:59:18","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=1395"},"modified":"2025-11-15T10:58:26","modified_gmt":"2025-11-15T03:58:26","slug":"alfentanil-hydrochloride-hydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/alfentanil-hydrochloride-hydrate\/","title":{"rendered":"Alfentanil Hydrochloride Hydrate"},"content":{"rendered":"

Alfentanil Hydrochloride<\/p>\n

(Ph. Eur. monograph 1062)<\/p>\n

C_{21<\/sub>H_{33<\/sub>ClN_{6<\/sub>O_{3<\/sub>, xH_{2<\/sub>O\u00a0 \u00a0 \u00a0453.0 (anhydrous substance)<\/p>\n}}}}}

Anhydrous alfentanil hydrochloride 69049-06-5<\/p>\n

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

Opioid receptor agonist; analgesic.<\/p>\n

DEFINITION<\/h2>\n
N-[1-[2-(4-Ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl]-N-phenylpropanamide hydrochloride hydrate.<\/p>\n
Content<\/h3>\n
98.5 per cent to 101.5 per cent (anhydrous substance).<\/p>\n
It contains a variable quantity of water.<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white powder.<\/p>\n
Solubility<\/h3>\n
Freely soluble in water, in ethanol (96 per cent) and in methanol.<\/p>\n
mp<\/h3>\n
About 140 \u00b0C, with decomposition.<\/p>\n
It shows polymorphism (5.9).<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: alfentanil hydrochloride hydrate CRS.<\/p>\n
If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substance separately in methanol R, evaporate to dryness and record new spectra using the residues.<\/p>\n
B. Dissolve 50 mg in a mixture of 0.4 mL of ammonia R and 2 mL of water R. Mix, allow to stand for 5 min and filter. Acidify the filtrate with dilute nitric acid R. It gives reaction (a) of chlorides (2.3.1).<\/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 0.2 g in water R and dilute to 20 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Carry out the test protected from light.<\/p>\n
Test 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): In order to prepare impurity E in situ, dissolve 10 mg of the substance to be examined in 10.0 mL of dilute hydrochloric acid R. Heat on a water-bath under a reflux condenser for 4 h. Neutralise with 10.0 mL of dilute sodium hydroxide solution R and evaporate to dryness on a water-bath. Cool and take up the residue in 10 mL of methanol R. Filter.<\/p>\n
Reference solution (b): Dissolve the contents of a vial of alfentanil impurity D CRS in 1 mL of methanol R.<\/p>\n
Reference solution (c): Dilute 1.0 mL of the test solution to 100.0 mL with methanol R. Dilute 1.0 mL of this solution to 10.0 mL with methanol R.<\/p>\n
Blank solution: methanol R.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.1 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (3 \u03bcm).<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: 5 g\/L solution of ammonium carbonate R in a mixture of 10 volumes of tetrahydrofuran R and 90 volumes of water for chromatography R;<\/p>\n
\u2014 mobile phase B: acetonitrile for chromatography R;<\/p>\n\n\n\n\n\n\n
Time<\/strong>
\n(min)<\/strong><\/td>\n Mobile phase A<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n Mobile phase B<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 15<\/td>\n \u00a090 \u2192 40<\/td>\n \u00a010 \u2192 60<\/td>\n<\/tr>\n
15 – 20<\/td>\n \u00a040<\/td>\n \u00a060<\/td>\n<\/tr>\n
20 – 25<\/td>\n \u00a040 \u2192 90<\/td>\n 60 \u2192 10<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.5 mL\/min.<\/p>\n
Detection: Spectrophotometer at 220 nm.<\/p>\n
Injection: 10 \u03bcL.<\/p>\n
Identification of impurities: Use the chromatogram obtained with reference solution (a) to identify the peak due to impurity E; use the chromatogram obtained with reference solution (b) to identify the peak due to impurity D.<\/p>\n
Relative retention: With reference to alfentanil (retention time = about 8 min): impurity D = about 0.8; impurity E = about 0.9.<\/p>\n
System suitability: Reference solution (a):<\/p>\n
\u2014 resolution: minimum 4.0 between the peaks due to impurity E and alfentanil.
\nCalculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of alfentanil hydrochloride hydrate in reference solution (c).<\/p>\n
Limits:<\/p>\n
\u2014 impurity D: maximum 0.2 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 0.4 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
Water (2.5.12)<\/h4>\n
3.0 per cent to 4.0 per cent, determined on 0.500 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.350 g in 50 mL of a mixture of 1 volume of ethanol (96 per cent) R and 4 volumes of water R and add 5.0 mL of 0.01 M hydrochloric acid. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20). Read the volume added between the 2 points of inflexion.<\/p>\n
1 mL of 0.1 M sodium hydroxide is equivalent to 45.30 mg of C_{21<\/sub>H_{33<\/sub>ClN_{6<\/sub>O_{3<\/sub>.<\/h2>\nSTORAGE<\/h2>\nProtected from light.<\/p>\n
IMPURITIES<\/h2>\nSpecified impurities 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 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. Control of impurities in substances for pharmaceutical use) A, B, C, E, F, G, H.<\/p>\n
<\/p>\n
A. (1s,4s)-1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-(N-phenylpropanamido)piperidine 1-oxide,<\/p>\n
<\/p>\n
B. (1r,4r)-1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-(N-phenylpropanamido)piperidine 1-oxide,<\/p>\n
<\/p>\n
C. N-[4-(methoxymethyl)piperidin-4-yl]-N-phenylpropanamide,<\/p>\n
<\/p>\n
D. N-[1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl]-N-phenylacetamide,<\/p>\n
<\/p>\n
E. 1-ethyl-4-[2-[4-(methoxymethyl)-4-(phenylamino)piperidin-1-yl]ethyl]-1,4-dihydro-5H-tetrazol-5-one,<\/p>\n
<\/p>\n
F. N-[1-(2-hydroxyethyl)-4-(methoxymethyl)piperidin-4-yl]-N-phenylpropanamide,<\/p>\n
<\/p>\n
G. N-[1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-[(propanoyloxy)methyl]piperidin-4-yl]-N-phenylpropanamide,<\/p>\n
<\/p>\n
H. N-[1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl]-N-phenylbutanamide.<\/p>\n","protected":false},"excerpt":{"rendered":"
Alfentanil Hydrochloride (Ph. Eur. monograph 1062) C21H33ClN6O3, xH2O\u00a0 \u00a0 \u00a0453.0 (anhydrous substance) Anhydrous alfentanil hydrochloride 69049-06-5 Action and use Opioid receptor agonist; analgesic. DEFINITION N-[1-[2-(4-Ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl]-N-phenylpropanamide hydrochloride hydrate. Content 98.5 per cent to 101.5 per cent (anhydrous substance). It contains a variable quantity of water. CHARACTERS Appearance White or almost white powder. Solubility Freely soluble in…<\/p>\n","protected":false},"author":2,"featured_media":1418,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-1395","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\/1395","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=1395"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1395\/revisions"}],"predecessor-version":[{"id":6926,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1395\/revisions\/6926"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/1418"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=1395"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=1395"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=1395"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}}}}}

Time<\/strong> \n(min)<\/strong><\/td>\n	Mobile phase A<\/strong> \n(per cent V\/V)<\/strong><\/td>\n	Mobile phase B<\/strong> \n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 15<\/td>\n	\u00a090 \u2192 40<\/td>\n	\u00a010 \u2192 60<\/td>\n<\/tr>\n
15 – 20<\/td>\n	\u00a040<\/td>\n	\u00a060<\/td>\n<\/tr>\n
20 – 25<\/td>\n	\u00a040 \u2192 90<\/td>\n	60 \u2192 10<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 1.5 mL\/min.<\/p>\n Detection: Spectrophotometer at 220 nm.<\/p>\n Injection: 10 \u03bcL.<\/p>\n Identification of impurities: Use the chromatogram obtained with reference solution (a) to identify the peak due to impurity E; use the chromatogram obtained with reference solution (b) to identify the peak due to impurity D.<\/p>\n Relative retention: With reference to alfentanil (retention time = about 8 min): impurity D = about 0.8; impurity E = about 0.9.<\/p>\n System suitability: Reference solution (a):<\/p>\n \u2014 resolution: minimum 4.0 between the peaks due to impurity E and alfentanil. \nCalculation of percentage contents:<\/p>\n \u2014 for each impurity, use the concentration of alfentanil hydrochloride hydrate in reference solution (c).<\/p>\n Limits:<\/p>\n \u2014 impurity D: maximum 0.2 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total: maximum 0.4 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent.<\/p>\n Water (2.5.12)<\/h4>\n 3.0 per cent to 4.0 per cent, determined on 0.500 g.<\/p>\n ASSAY<\/h2>\n Dissolve 0.350 g in 50 mL of a mixture of 1 volume of ethanol (96 per cent) R and 4 volumes of water R and add 5.0 mL of 0.01 M hydrochloric acid. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20). Read the volume added between the 2 points of inflexion.<\/p>\n 1 mL of 0.1 M sodium hydroxide is equivalent to 45.30 mg of C_{21<\/sub>H_{33<\/sub>ClN_{6<\/sub>O_{3<\/sub>.<\/h2>\nSTORAGE<\/h2>\nProtected from light.<\/p>\n IMPURITIES<\/h2>\nSpecified impurities 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 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. Control of impurities in substances for pharmaceutical use) A, B, C, E, F, G, H.<\/p>\n <\/p>\n A. (1s,4s)-1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-(N-phenylpropanamido)piperidine 1-oxide,<\/p>\n <\/p>\n B. (1r,4r)-1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-(N-phenylpropanamido)piperidine 1-oxide,<\/p>\n <\/p>\n C. N-[4-(methoxymethyl)piperidin-4-yl]-N-phenylpropanamide,<\/p>\n <\/p>\n D. N-[1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl]-N-phenylacetamide,<\/p>\n <\/p>\n E. 1-ethyl-4-[2-[4-(methoxymethyl)-4-(phenylamino)piperidin-1-yl]ethyl]-1,4-dihydro-5H-tetrazol-5-one,<\/p>\n <\/p>\n F. N-[1-(2-hydroxyethyl)-4-(methoxymethyl)piperidin-4-yl]-N-phenylpropanamide,<\/p>\n <\/p>\n G. N-[1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-[(propanoyloxy)methyl]piperidin-4-yl]-N-phenylpropanamide,<\/p>\n <\/p>\n H. N-[1-[2-(4-ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl]-N-phenylbutanamide.<\/p>\n","protected":false},"excerpt":{"rendered":" Alfentanil Hydrochloride (Ph. Eur. monograph 1062) C21H33ClN6O3, xH2O\u00a0 \u00a0 \u00a0453.0 (anhydrous substance) Anhydrous alfentanil hydrochloride 69049-06-5 Action and use Opioid receptor agonist; analgesic. DEFINITION N-[1-[2-(4-Ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl]-N-phenylpropanamide hydrochloride hydrate. Content 98.5 per cent to 101.5 per cent (anhydrous substance). It contains a variable quantity of water. CHARACTERS Appearance White or almost white powder. Solubility Freely soluble in…<\/p>\n","protected":false},"author":2,"featured_media":1418,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-1395","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\/1395","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=1395"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1395\/revisions"}],"predecessor-version":[{"id":6926,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/1395\/revisions\/6926"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/1418"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=1395"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=1395"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=1395"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}}}}}

Content<\/h3>\n98.5 per cent to 101.5 per cent (anhydrous substance).<\/p>\nIt contains a variable quantity of water.<\/p>\n

CHARACTERS<\/h2>\n

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

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

mp<\/h3>\nAbout 140 \u00b0C, with decomposition.<\/p>\nIt shows polymorphism (5.9).<\/p>\n

TESTS<\/h2>\n

Appearance of solution<\/h3>\nThe solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\nDissolve 0.2 g in water R and dilute to 20 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\n3.0 per cent to 4.0 per cent, determined on 0.500 g.<\/p>\n

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

Content<\/h3>\n
98.5 per cent to 101.5 per cent (anhydrous substance).<\/p>\n
It contains a variable quantity of water.<\/p>\n

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

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

mp<\/h3>\n
About 140 \u00b0C, with decomposition.<\/p>\n
It shows polymorphism (5.9).<\/p>\n

Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n
Dissolve 0.2 g in water R and dilute to 20 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\n
3.0 per cent to 4.0 per cent, determined on 0.500 g.<\/p>\n

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