{"id":11721,"date":"2025-10-10T09:01:36","date_gmt":"2025-10-10T02:01:36","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=11721"},"modified":"2025-10-10T09:01:36","modified_gmt":"2025-10-10T02:01:36","slug":"fentanyl-citrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/fentanyl-citrate\/","title":{"rendered":"Fentanyl Citrate"},"content":{"rendered":"

(Ph. Eur. monograph 1103)<\/p>\n

C_{28<\/sub>H_{36<\/sub>N_{2<\/sub>O_{8<\/sub>\u00a0 \u00a0528.6\u00a0 \u00a0990-73-8<\/p>\n}}}}

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

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

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

Bupivacaine and Fentanyl Injection<\/p>\n

Fentanyl Injection<\/p>\n

DEFINITION<\/h2>\n
N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate.<\/p>\n
Content<\/h3>\n
99.0 per cent to 101.0 per cent (dried substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white powder.<\/p>\n
Solubility<\/h3>\n
Soluble in water, freely soluble in methanol, sparingly soluble in ethanol (96 per cent), very slightly soluble in methylene chloride.<\/p>\n
mp<\/h3>\n
About 152 \u00b0C, with decomposition.<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison fentanyl citrate 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 0.2 g of the substance to be examined in water R and dilute to 20 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Solvent mixture methanol R, water R (50:50 V\/V).<\/p>\n
Test solution Dissolve 39.3 mg of the substance to be examined in 2.5 mL of methanol R and dilute to 5.0 mL with water R.<\/p>\n
Reference solution (a) Dilute 1.0 mL of the test solution to 10.0 mL with the solvent mixture. Dissolve the contents of a vial of fentanyl impurity mixture CRS (impurities C and D) in 1.0 mL of this solution, using sonication for 1 min if necessary.<\/p>\n
Reference solution (b) Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 2.1 mm;<\/p>\n
\u2014 stationary phase: end-capped ethylene-bridged phenylsilyl silica gel for chromatography (hybrid material) R (1.7 \u03bcm);<\/p>\n
\u2014 temperature: 45 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: dissolve 0.8 g of ammonium acetate R in water for chromatography R, add 2 mL of trifluoroacetic acid R and dilute to 1000.0 mL with water for chromatography R;<\/p>\n
\u2014 mobile phase B: add 2 mL of trifluoroacetic acid R to 950 mL of acetonitrile R1 and shake to homogenise; dissolve 0.8 g of ammonium acetate R in this solution and shake until complete dissolution, then dilute to 1000.0 mL with acetonitrile R1;<\/p>\n\n\n\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 – 1<\/td>\n 98<\/td>\n 2<\/td>\n<\/tr>\n
1 – 5<\/td>\n 98 \u2192 90<\/td>\n 2 \u2192 10<\/td>\n<\/tr>\n
5 – 17<\/td>\n 90 \u2192 70<\/td>\n 10 \u2192 30<\/td>\n<\/tr>\n
17 – 30<\/td>\n 70 \u2192 5<\/td>\n 30 \u2192 95<\/td>\n<\/tr>\n
30 – 31<\/td>\n 5<\/td>\n 95<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate 0.35 mL\/min.<\/p>\n
Detection Spectrophotometer at 210 nm.<\/p>\n
Injection 5 \u03bcL.<\/p>\n
Identification of impurities Use the chromatogram supplied with fentanyl impurity mixture CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities C and D.<\/p>\n
Relative retention With reference to fentanyl (retention time = about 19 min): impurity D = about 0.8; impurity C = about 0.9.<\/p>\n
System suitability Reference solution (a):<\/p>\n
\u2014 resolution: minimum 5.0 between the peaks due to impurity C and fentanyl.<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of fentanyl citrate in reference solution (b).<\/p>\n
Limits:<\/p>\n
\u2014 impurities C, D: for each impurity, maximum 0.15 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
Loss on drying (2.2.32)<\/h4>\n
Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 60 \u00b0C.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.300 g in 50 mL of a mixture of 1 volume of anhydrous acetic acid R and 7 volumes of methyl ethyl ketone R.<\/p>\n
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 52.86 mg of C_{28<\/sub>H_{36<\/sub>N_{2<\/sub>O_{8<\/sub>.<\/p>\n}}}}
STORAGE<\/h2>\n
Protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities 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 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, E, F, G,H, I.<\/p>\n
$\"Fentanyl$ <\/p>\n
A. (1rs,4rs)-1-(2-phenylethyl)-4-(N-phenylpropanamido)piperidine N-oxide,<\/p>\n
$\"Fentanyl$ <\/p>\n
B. N-phenyl-N-(piperidin-4-yl)propanamide,<\/p>\n
$\"Fentanyl$ <\/p>\n
C. N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide,<\/p>\n
$\"Fentanyl$ <\/p>\n
D. N-phenyl-1-(2-phenylethyl)piperidin-4-amine,<\/p>\n
$\"Fentanyl$ <\/p>\n
E. benzaldehyde,<\/p>\n
$\"Fentanyl$ <\/p>\n
F. N-phenylpiperidin-4-amine,<\/p>\n
$\"Fentanyl$ <\/p>\n
G. 1-benzyl-N-phenylpiperidin-4-amine,<\/p>\n
$\"Fentanyl$ <\/p>\n
H. N-(1-benzylpiperidin-4-yl)-N-phenylpropanamide,<\/p>\n
$\"Fentanyl$ <\/p>\n
I. (2-bromoethyl)benzene.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 1103) C28H36N2O8\u00a0 \u00a0528.6\u00a0 \u00a0990-73-8 Action and use Opioid receptor agonist; analgesic. Preparations Bupivacaine and Fentanyl Injection Fentanyl Injection DEFINITION N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white powder. Solubility Soluble in water, freely soluble in methanol, sparingly soluble in ethanol (96…<\/p>\n","protected":false},"author":3,"featured_media":11750,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-11721","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\/11721","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=11721"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/11721\/revisions"}],"predecessor-version":[{"id":11759,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/11721\/revisions\/11759"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/11750"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=11721"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=11721"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=11721"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

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 – 1<\/td>\n	98<\/td>\n	2<\/td>\n<\/tr>\n
1 – 5<\/td>\n	98 \u2192 90<\/td>\n	2 \u2192 10<\/td>\n<\/tr>\n
5 – 17<\/td>\n	90 \u2192 70<\/td>\n	10 \u2192 30<\/td>\n<\/tr>\n
17 – 30<\/td>\n	70 \u2192 5<\/td>\n	30 \u2192 95<\/td>\n<\/tr>\n
30 – 31<\/td>\n	5<\/td>\n	95<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate 0.35 mL\/min.<\/p>\n Detection Spectrophotometer at 210 nm.<\/p>\n Injection 5 \u03bcL.<\/p>\n Identification of impurities Use the chromatogram supplied with fentanyl impurity mixture CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities C and D.<\/p>\n Relative retention With reference to fentanyl (retention time = about 19 min): impurity D = about 0.8; impurity C = about 0.9.<\/p>\n System suitability Reference solution (a):<\/p>\n \u2014 resolution: minimum 5.0 between the peaks due to impurity C and fentanyl.<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 for each impurity, use the concentration of fentanyl citrate in reference solution (b).<\/p>\n Limits:<\/p>\n \u2014 impurities C, D: for each impurity, maximum 0.15 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 Loss on drying (2.2.32)<\/h4>\n Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 60 \u00b0C.<\/p>\n ASSAY<\/h2>\n Dissolve 0.300 g in 50 mL of a mixture of 1 volume of anhydrous acetic acid R and 7 volumes of methyl ethyl ketone R.<\/p>\n 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 52.86 mg of C_{28<\/sub>H_{36<\/sub>N_{2<\/sub>O_{8<\/sub>.<\/p>\n}}}} STORAGE<\/h2>\n Protected from light.<\/p>\n IMPURITIES<\/h2>\n Specified impurities 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 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, E, F, G,H, I.<\/p>\n $\"Fentanyl$ <\/p>\n A. (1rs,4rs)-1-(2-phenylethyl)-4-(N-phenylpropanamido)piperidine N-oxide,<\/p>\n $\"Fentanyl$ <\/p>\n B. N-phenyl-N-(piperidin-4-yl)propanamide,<\/p>\n $\"Fentanyl$ <\/p>\n C. N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide,<\/p>\n $\"Fentanyl$ <\/p>\n D. N-phenyl-1-(2-phenylethyl)piperidin-4-amine,<\/p>\n $\"Fentanyl$ <\/p>\n E. benzaldehyde,<\/p>\n $\"Fentanyl$ <\/p>\n F. N-phenylpiperidin-4-amine,<\/p>\n $\"Fentanyl$ <\/p>\n G. 1-benzyl-N-phenylpiperidin-4-amine,<\/p>\n $\"Fentanyl$ <\/p>\n H. N-(1-benzylpiperidin-4-yl)-N-phenylpropanamide,<\/p>\n $\"Fentanyl$ <\/p>\n I. (2-bromoethyl)benzene.<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 1103) C28H36N2O8\u00a0 \u00a0528.6\u00a0 \u00a0990-73-8 Action and use Opioid receptor agonist; analgesic. Preparations Bupivacaine and Fentanyl Injection Fentanyl Injection DEFINITION N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white powder. Solubility Soluble in water, freely soluble in methanol, sparingly soluble in ethanol (96…<\/p>\n","protected":false},"author":3,"featured_media":11750,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-11721","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\/11721","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=11721"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/11721\/revisions"}],"predecessor-version":[{"id":11759,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/11721\/revisions\/11759"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/11750"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=11721"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=11721"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=11721"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

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

Solubility<\/h3>\nSoluble in water, freely soluble in methanol, sparingly soluble in ethanol (96 per cent), very slightly soluble in methylene chloride.<\/p>\n

mp<\/h3>\nAbout 152 \u00b0C, with decomposition.<\/p>\n

IDENTIFICATION<\/h2>\nInfrared absorption spectrophotometry (2.2.24).<\/p>\nComparison fentanyl citrate CRS.<\/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 of the substance to be examined in water R and dilute to 20 mL with the same solvent.<\/p>\n

Loss on drying (2.2.32)<\/h4>\nMaximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 60 \u00b0C.<\/p>\n

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

Content<\/h3>\n
99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

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

Solubility<\/h3>\n
Soluble in water, freely soluble in methanol, sparingly soluble in ethanol (96 per cent), very slightly soluble in methylene chloride.<\/p>\n

mp<\/h3>\n
About 152 \u00b0C, with decomposition.<\/p>\n

IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison fentanyl citrate CRS.<\/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 of the substance to be examined in water R and dilute to 20 mL with the same solvent.<\/p>\n

Loss on drying (2.2.32)<\/h4>\n
Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 60 \u00b0C.<\/p>\n

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