{"id":15718,"date":"2025-10-18T10:24:40","date_gmt":"2025-10-18T03:24:40","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=15718"},"modified":"2025-11-15T15:50:30","modified_gmt":"2025-11-15T08:50:30","slug":"haloperidol-decanoate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/haloperidol-decanoate\/","title":{"rendered":"Haloperidol Decanoate"},"content":{"rendered":"

(Ph. Eur. monograph 1431)<\/em><\/p>\n

C_{31<\/sub>H_{41<\/sub>ClFNO_{3<\/sub> 530.1 74050-97-8<\/p>\n}}}

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

Dopamine receptor antagonist; neuroleptic.<\/p>\n

DEFINITION<\/h2>\n
4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate.<\/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 powder.<\/p>\n
Solubility<\/h3>\n
Practically insoluble in water, very soluble in ethanol (96 per cent), in methanol and in methylene chloride.<\/p>\n
mp<\/h3>\n
About 42 \u00b0C.<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: haloperidol decanoate CRS.<\/p>\n
B. To 0.1 g in a porcelain crucible add 0.5 g of anhydrous sodium carbonate R. Heat over an open flame for 10 min.<\/p>\n
Allow to cool. Take up the residue with 5 mL of dilute nitric acid R and filter. To 1 mL of the filtrate add 1 mL of water R. The solution 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 not more intensely coloured than reference solution B5 (2.2.2, Method II).<\/p>\n
Dissolve 2.0 g in methylene chloride R and dilute to 20 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Prepare the solutions immediately before use and protect 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): Dissolve 10 mg of haloperidol decanoate for system suitability CRS (containing impurities B, D and I) in methanol R and dilute to 1 mL with the same solvent.<\/p>\n
Reference solution (b): Dissolve the contents of a vial of haloperidol decanoate impurity mixture CRS (impurities H, J and K) 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
Column:<\/p>\n
\u2014 size: l = 0.10 m, \u00d8 = 4.0 mm;<\/p>\n
\u2014 stationary phase: base-deactivated end-capped octadecylsilyl silica gel for chromatography R (3 \u03bcm).<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: 27 g\/L solution of tetrabutylammonium hydrogen sulfate R;<\/p>\n
\u2014 mobile phase B: acetonitrile for chromatography R;<\/p>\n\n\n\n\n\n
Time<\/strong><\/p>\n
(min)<\/strong><\/td>\n
Mobile phase A<\/strong><\/p>\n
(per cent V\/V)<\/strong><\/td>\n
Mobile phase B<\/strong><\/p>\n
(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 30<\/td>\n 80 \u2192 40<\/td>\n 20 \u2192 60<\/td>\n<\/tr>\n
30 – 35<\/td>\n 40<\/td>\n 60<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.5 mL\/min.<\/p>\n
Detection: Spectrophotometer at 230 nm.<\/p>\n
Injection: 10 \u03bcL.<\/p>\n
Identification of impurities: Use the chromatogram supplied with haloperidol decanoate for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities B, D and I; use the chromatogram supplied with haloperidol decanoate impurity mixture CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities H, J and K.<\/p>\n
Relative retention: With reference to haloperidol decanoate (retention time = about 24 min): impurity H = about 0.80; impurity I =about 0.88; impurity B = about 0.98; impurity J = about 1.1; impurity D = about 1.20; impurity K = about 1.22.<\/p>\n
System suitability Reference solution (a):<\/p>\n
\u2014 peak-to-valley ratio: minimum 1.5, where Hp = height above the baseline of the peak due to impurity B and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to haloperidol decanoate.<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of haloperidol decanoate in reference solution (c).<\/p>\n
Limits:<\/p>\n
\u2014 impurity D: maximum 0.5 per cent;<\/p>\n
\u2014 impurities B, H, I, J, K: for each impurity, maximum 0.3 per cent;\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 1.0 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
Loss on drying (2.2.32)<\/h3>\n
Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 30 \u00b0C.<\/p>\n
Sulfated ash (2.4.14)<\/h3>\n
Maximum 0.1 per cent, determined on 1.0 g in a platinum crucible.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.425 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, using 0.2 mL of naphtholbenzein solution R as indicator.<\/p>\n
1 mL of 0.1 M perchloric acid is equivalent to 53.01 mg of C_{31<\/sub>H_{41<\/sub>ClFNO_{3<\/sub>.<\/p>\n}}}
STORAGE<\/h2>\n
Protected from light, at a temperature below 25 \u00b0C.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities B, D, H, I, J, K.<\/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, C, E, F, G, L.<\/p>\n
$\"Haloperidol$ <\/p>\n
A. 1-[4-(4-fluorophenyl)-4-oxobutyl]-4-phenylpiperidin-4-yl decanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
B. 4-(4-chlorophenyl)-1-[4-(2-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
C. 4-(4-chlorophenyl)-1-[4-(3-ethyl-4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
D. 1 ,9 -dichloro-2 -hydroxy-4-oxo-2(4,1),8(1,4)-piperidina-1,9(1),3(1,4)-tribenzenanonaphan-8 -yl decanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
E. 1 -chloro-8 -fluoro-7-oxo-3(4,1)-piperidina-1,8(1),2(1,4)-tribenzenaoctaphan-3 -yl decanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
F. 1 -chloro-8 -fluoro-7-oxo-3(4,1)-piperidina-1,8(1),2(1,4)-tribenzenaoctaphan-3 -yl decanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
G. 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one (haloperidol),<\/p>\n
$\"Haloperidol$ <\/p>\n
H. 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl octanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
I. 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl nonanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
J. 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl undecanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
K. 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl dodecanoate,<\/p>\n
$\"Haloperidol$ <\/p>\n
L. 1-(4-fluorophenyl)ethan-1-one.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 1431) C31H41ClFNO3 530.1 74050-97-8 Action and use Dopamine receptor antagonist; neuroleptic. DEFINITION 4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate. Content 98.5 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white powder. Solubility Practically insoluble in water, very soluble in ethanol (96 per cent), in methanol and in methylene chloride. mp About 42…<\/p>\n","protected":false},"author":4,"featured_media":15846,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-15718","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\/15718","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=15718"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/15718\/revisions"}],"predecessor-version":[{"id":32177,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/15718\/revisions\/32177"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/15846"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=15718"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=15718"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=15718"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n98.5 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>\nPractically insoluble in water, very soluble in ethanol (96 per cent), in methanol and in methylene chloride.<\/p>\n

mp<\/h3>\nAbout 42 \u00b0C.<\/p>\n

TESTS<\/h2>\n

Appearance of solution<\/h3>\nThe solution is clear (2.2.1) and not more intensely coloured than reference solution B5 (2.2.2, Method II).<\/p>\nDissolve 2.0 g in methylene chloride R and dilute to 20 mL with the same solvent.<\/p>\n

Loss on drying (2.2.32)<\/h3>\nMaximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 30 \u00b0C.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\nMaximum 0.1 per cent, determined on 1.0 g in a platinum crucible.<\/p>\n

STORAGE<\/h2>\nProtected from light, at a temperature below 25 \u00b0C.<\/p>\n

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

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

Solubility<\/h3>\n
Practically insoluble in water, very soluble in ethanol (96 per cent), in methanol and in methylene chloride.<\/p>\n

mp<\/h3>\n
About 42 \u00b0C.<\/p>\n

Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and not more intensely coloured than reference solution B5 (2.2.2, Method II).<\/p>\n
Dissolve 2.0 g in methylene chloride R and dilute to 20 mL with the same solvent.<\/p>\n

Loss on drying (2.2.32)<\/h3>\n
Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 30 \u00b0C.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\n
Maximum 0.1 per cent, determined on 1.0 g in a platinum crucible.<\/p>\n

STORAGE<\/h2>\n
Protected from light, at a temperature below 25 \u00b0C.<\/p>\n