{"id":13202,"date":"2025-10-13T11:09:00","date_gmt":"2025-10-13T04:09:00","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=13202"},"modified":"2025-10-13T11:09:00","modified_gmt":"2025-10-13T04:09:00","slug":"flunarizine-dihydrochloride","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/flunarizine-dihydrochloride\/","title":{"rendered":"Flunarizine Dihydrochloride"},"content":{"rendered":"

(Ph. Eur. monograph 1722)<\/p>\n

C_{26<\/sub>H_{28<\/sub>Cl_{2<\/sub>F_{2<\/sub>N_{2<\/sub>\u00a0 \u00a0 \u00a0 477.4\u00a0 \u00a0 \u00a0 \u00a030484-77-6<\/p>\n}}}}}

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

Calcium channel blocker.<\/p>\n

DEFINITION<\/h2>\n
1-[Bis(4-fluorophenyl)methyl]-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine dihydrochloride.<\/p>\n
Content<\/h3>\n
99.0 per cent to 101.5 per cent (dried substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white powder, hygroscopic.<\/p>\n
Solubility<\/h3>\n
Slightly soluble in water, sparingly soluble in methanol, slightly soluble in ethanol (96 per cent) and in methylene chloride.<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: flunarizine dihydrochloride CRS.<\/p>\n
B. Dissolve 25 mg in 2 mL of methanol R and add 0.5 mL of water R. The solution gives reaction (a) of chlorides (2.3.1).<\/p>\n
TESTS<\/h2>\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 flunarizine for system suitability CRS (containing impurities B and C) in methanol R and dilute to 1 mL with the same solvent.<\/p>\n
Reference solution (b): 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 = 4.6 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: solution containing 23.8 g\/L of tetrabutylammonium hydrogen sulfate R and 7 g\/L of ammonium acetate R;<\/p>\n
\u2014 mobile phase B: acetonitrile for chromatography R;<\/p>\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 – 12<\/td>\n 80 \u2192 40<\/td>\n 20 \u2192 60<\/td>\n<\/tr>\n
12 – 15<\/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 flunarizine for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities B and C.<\/p>\n
Relative retention: With reference to flunarizine (retention time = about 8 min): impurity B = about 0.93; impurity C = about 0.96.<\/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 C and H_{v<\/sub> = height above the baseline of the lowest point of the curve separating this peak from the peak due to flunarizine.<\/p>\n}
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of flunarizine dihydrochloride in reference solution (b).<\/p>\n
Limits:<\/p>\n
\u2014 impurity B: maximum 0.3 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 0.5 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
Loss on drying (2.2.32)<\/h4>\n
Maximum 5.0 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 4 h.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g in a platinum crucible.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.200 g in 70 mL of ethanol (96 per cent) R. Carry out a potentiometric titration (2.2.20), using 0.1 M sodium hydroxide. Read the volume added at the second point of inflexion. Carry out a blank titration.<\/p>\n
1 mL of 0.1 M sodium hydroxide is equivalent to 23.87 mg of C_{26<\/sub>H_{28<\/sub>Cl_{2<\/sub>F_{2<\/sub>N_{2<\/sub>.<\/p>\n}}}}}
STORAGE<\/h2>\n
In an airtight container, protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities B.<\/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, D.<\/p>\n
$\"Flunarizine$ <\/p>\n
A. 1-[bis(4-fluorophenyl)methyl]piperazine,<\/p>\n
$\"Flunarizine$ <\/p>\n
B. 1-[(RS)-(4-fluorophenyl)phenylmethyl]-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine,<\/p>\n
$\"Flunarizine$ <\/p>\n
C. 1-[(RS)-(2-fluorophenyl)(4-fluorophenyl)methyl]-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine,<\/p>\n
$\"Flunarizine$ <\/p>\n
D. 1-[bis(4-fluorophenyl)methyl]-4-[(2Z)-3-phenylprop-2-en-1-yl]piperazine.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 1722) C26H28Cl2F2N2\u00a0 \u00a0 \u00a0 477.4\u00a0 \u00a0 \u00a0 \u00a030484-77-6 Action and use Calcium channel blocker. DEFINITION 1-[Bis(4-fluorophenyl)methyl]-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine dihydrochloride. Content 99.0 per cent to 101.5 per cent (dried substance). CHARACTERS Appearance White or almost white powder, hygroscopic. Solubility Slightly soluble in water, sparingly soluble in methanol, slightly soluble in ethanol (96 per cent) and…<\/p>\n","protected":false},"author":2,"featured_media":13214,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-13202","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\/13202","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=13202"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13202\/revisions"}],"predecessor-version":[{"id":13218,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13202\/revisions\/13218"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/13214"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=13202"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=13202"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=13202"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n99.0 per cent to 101.5 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

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

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

IDENTIFICATION<\/h2>\nA. Infrared absorption spectrophotometry (2.2.24).<\/p>\nComparison: flunarizine dihydrochloride CRS.<\/p>\nB. Dissolve 25 mg in 2 mL of methanol R and add 0.5 mL of water R. The solution gives reaction (a) of chlorides (2.3.1).<\/p>\n

TESTS<\/h2>\n

Loss on drying (2.2.32)<\/h4>\nMaximum 5.0 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 4 h.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.1 per cent, determined on 1.0 g in a platinum crucible.<\/p>\n

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

Content<\/h3>\n
99.0 per cent to 101.5 per cent (dried substance).<\/p>\n

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

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

IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: flunarizine dihydrochloride CRS.<\/p>\n
B. Dissolve 25 mg in 2 mL of methanol R and add 0.5 mL of water R. The solution gives reaction (a) of chlorides (2.3.1).<\/p>\n

Loss on drying (2.2.32)<\/h4>\n
Maximum 5.0 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 4 h.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g in a platinum crucible.<\/p>\n

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