{"id":25610,"date":"2025-11-04T16:03:40","date_gmt":"2025-11-04T09:03:40","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=25610"},"modified":"2025-11-04T16:14:20","modified_gmt":"2025-11-04T09:14:20","slug":"naftidrofuryl-oxalate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/naftidrofuryl-oxalate\/","title":{"rendered":"Naftidrofuryl Oxalate"},"content":{"rendered":"

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

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

Vasodilator.<\/p>\n

Preparation<\/strong><\/p>\n

Naftidrofuryl Capsules<\/p>\n

Ph Eur<\/p>\n

\n
DEFINITION<\/h2>\n
Mixture of 4 stereoisomers of 2-(diethylamino)ethyl 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2- yl)propanoate hydrogen oxalate.<\/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 powder.<\/p>\n
Solubility<\/strong><\/p>\n
Freely soluble in water, freely soluble or soluble in ethanol (96 per cent), slightly or sparingly soluble in acetone.<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Preparation\u00a0 Dissolve 1.0 g in water R and dilute to 50 mL with the same solvent. Add 2 mL of concentrated ammonia R and shake with 3 quantities, each of 10 mL, of methylene chloride R. To the combined lower layers, add anhydrous sodium sulfate R, shake, filter and evaporate the filtrate by suitable means at a temperature not exceeding 30 \u00b0C. Use the residue obtained.<\/p>\n
Comparison\u00a0 Ph. Eur. reference spectrum of naftidrofuryl.<\/p>\n
B. Dissolve 0.5 g in water R and dilute to 10 mL with the same solvent. Add 2.0 mL of calcium chloride solution R. A white precipitate is formed. The precipitate dissolves after the addition of 3.0 mL of hydrochloric acid R.<\/p>\n
TESTS<\/h2>\n
Absorbance (2.2.25)<\/h3>\n
Maximum 0.1 at 430 nm.<\/p>\n
Dissolve 1.5 g in water R and dilute to 10 mL with the same solvent. If necessary use an ultrasonic bath.<\/p>\n
Related substances<\/h3>\n
A. Liquid chromatography (2.2.29).<\/p>\n
Test solution\u00a0<\/em> Dissolve 80.0 mg of the substance to be examined in the mobile phase and dilute to 20.0 mL with the mobile phase. Sonicate for 10 s. A precipitate is formed. Filter through a membrane filter (nominal pore size 0.45 \u00b5m), discarding the first 5 mL. Use a freshly prepared solution.<\/p>\n
Reference solution (a)\u00a0<\/em> Dissolve 5.0 mg of naftidrofuryl impurity A CRS in acetonitrile R and dilute to 25.0 mL with the same solvent. Dilute 1.0 mL of the solution to 50.0 mL with the mobile phase.<\/p>\n
Reference solution (b)\u00a0<\/em> Dissolve 5 mg of naftidrofuryl impurity B CRS and 5 mg of the substance to be examined in acetonitrile R and dilute to 50 mL with the same solvent. Dilute 1 mL of the solution to 50 mL with the mobile phase.<\/p>\n
Column:<\/em><\/p>\n
\u2014 size: l<\/em> = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase:<\/em> end-capped octadecylsilyl silica gel for chromatography R (5 \u00b5m).<\/p>\n
Mobile phase<\/em>\u00a0 Mix 60 mL of methanol R with 150 mL of tetrabutylammonium buffer solution pH 7.0 R and dilute to 1000 mL with acetonitrile R.<\/p>\n
Flow rate\u00a0<\/em> 1 mL\/min.<\/p>\n
Detection\u00a0<\/em> Spectrophotometer at 283 nm.<\/p>\n
Injection\u00a0<\/em> 20 \u00b5L.<\/p>\n
Run time<\/em>\u00a0 2.3 times the retention time of naftidrofuryl.<\/p>\n
Relative retention<\/em>\u00a0 With reference to naftidrofuryl (retention time = about 7 min): impurity A = about 0.5; impurity B = about 0.8; impurity C = about 1.8.<\/p>\n
System suitability\u00a0<\/em> Reference solution (b):<\/p>\n
\u2014 resolution:<\/em> minimum 3.0 between the peaks due to impurity B and naftidrofuryl.<\/p>\n
Limits:<\/em><\/p>\n
\u2014 impurities A, B, C:<\/em> for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 per cent);<\/p>\n
\u2014 any other impurity:<\/em> for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 per cent);<\/p>\n
\u2014 total:<\/em> not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.3 per cent);<\/p>\n
\u2014 disregard limit:<\/em> 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.02 per cent).<\/p>\n
B. Gas chromatography (2.2.28).<\/p>\n
Test solution (a)\u00a0<\/em> Dissolve 1.0 g of the substance to be examined in water R and dilute to 50 mL with the same solvent. Add 2 mL of concentrated ammonia R and shake with 3 quantities, each of 10 mL, of methylene chloride R. To the combined lower layers, add anhydrous sodium sulfate R, shake, filter and evaporate the filtrate by suitable means at a temperature not exceeding 30 \u00b0C. Take up the residue with methylene chloride R and dilute to 20.0 mL with the same solvent.<\/p>\n
Test solution (b)\u00a0<\/em> Dilute 1.0 mL of test solution (a) to 10.0 mL with methylene chloride R.<\/p>\n
Reference solution\u00a0<\/em> Dissolve 5 mg of naftidrofuryl impurity F CRS in methylene chloride R and dilute to 50 mL with the same solvent.<\/p>\n
Column:<\/p>\n
\u2014 material:<\/em> fused silica;<\/p>\n
\u2014 size: l<\/em> = 25 m, \u00d8 = 0.32 mm;<\/p>\n
\u2014 stationary phase:<\/em> phenyl(5)methyl(95)polysiloxane R (film thickness 0.45 \u00b5m).<\/p>\n
Carrier gas helium for chromatography R. Splitter flow rate 25 mL\/min.<\/p>\n
Flow rate\u00a0<\/em> 2.9 mL\/min.<\/p>\n
Temperature:<\/em><\/p>\n\n\n\n\n\n\n\n\n\n
<\/td>\n Time (min)<\/strong><\/td>\n Temperature (\u00b0C)<\/strong><\/td>\n<\/tr>\n
Column<\/td>\n 0 – 4<\/td>\n 210<\/td>\n<\/tr>\n
4 – 8<\/td>\n 210 \u2192 230<\/td>\n<\/tr>\n
8 – 18<\/td>\n 230 \u2192 260<\/td>\n<\/tr>\n
18 – 30<\/td>\n 260<\/td>\n<\/tr>\n
Injection port<\/td>\n 290<\/td>\n<\/tr>\n
Detector<\/td>\n 290<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Detection<\/em>\u00a0 Flame ionisation.<\/p>\n
Injection<\/em>\u00a0 1 \u00b5L.<\/p>\n
Relative retention<\/em>\u00a0 With reference to the second eluting peak of naftidrofuryl: impurity D = about 0.14; impurity B = about 0.55 (for the second eluting peak); impurity E = about 0.86; impurity F = about 1.04 (for the second eluting peak).<\/p>\n
System suitability\u00a0<\/em> Test solution (b):<\/p>\n
\u2014 resolution:<\/em> minimum 1.0 between the 2 peaks due to the diastereoisomers of naftidrofuryl.<\/p>\n
Limits\u00a0 Test solution (a):<\/p>\n
\u2014 impurity F: for the sum of the areas of the 2 peaks, maximum 0.20 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.20 per cent);<\/p>\n
\u2014 impurity E: maximum 0.20 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.20 per cent);<\/p>\n
\u2014 impurity D: maximum 0.10 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.10 per cent);<\/p>\n
\u2014 any other impurity: for each impurity, maximum 0.10 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.10 per cent);<\/p>\n
\u2014 total: maximum 0.50 per cent of the sum of the areas of the 2 peaks due to naftidroduryl (0.50 per cent);<\/p>\n
\u2014 disregard limit: 0.02 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.02 per cent); disregard any peaks due to impurity B.<\/p>\n
Diastereoisomer ratio<\/p>\n
Gas chromatography (2.2.28) as described in test B for related substances.<\/p>\n
Limits\u00a0 Test solution (b):<\/p>\n
\u2014 first eluting naftidrofuryl diastereoisomer: minimum 30 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl.<\/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 0.350 g in 50 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).
\n1 mL of 0.1 M perchloric acid is equivalent to 47.36 mg of C26H35NO7.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities\u00a0 A, B, C, D, E, F.<\/p>\n
$\"Naftidrofuryl$ <\/p>\n
A. 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2-yl)propanoic acid,<\/p>\n
$\"Naftidrofuryl$ <\/p>\n
B. ethyl 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2-yl)propanoate,<\/p>\n
$\"Naftidrofuryl$ <\/p>\n
C. 2-(diethylamino)ethyl 3-(naphthalen-1-yl)-2-[(naphthalen-1-yl)methyl]propanoate,<\/p>\n
$\"Naftidrofuryl$ <\/p>\n
D. 2-(diethylamino)ethyl 3-[(2RS)-tetrahydrofuran-2-yl]propanoate,<\/p>\n
$\"Naftidrofuryl$ <\/p>\n
E. 2-(diethylamino)ethyl\u00a0 (2RS)-2-[(furan-2-yl)methyl]-3-(naphthalen-1-yl)propanoate,<\/p>\n
$\"Naftidrofuryl$ <\/p>\n
F. 2-(diethylamino)ethyl\u00a0 2-[(naphthalen-2-yl)methyl]-3-(tetrahydrofuran-2-yl)propanoate.<\/p>\n
\n
Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":"
Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Vasodilator. Preparation Naftidrofuryl Capsules Ph Eur DEFINITION Mixture of 4 stereoisomers of 2-(diethylamino)ethyl 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2- yl)propanoate hydrogen oxalate. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white powder. Solubility Freely soluble in water, freely soluble or soluble in ethanol…<\/p>\n","protected":false},"author":5,"featured_media":25611,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-25610","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-volumes-1-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25610","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=25610"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25610\/revisions"}],"predecessor-version":[{"id":25652,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25610\/revisions\/25652"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25611"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25610"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25610"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25610"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

<\/td>\n	Time (min)<\/strong><\/td>\n	Temperature (\u00b0C)<\/strong><\/td>\n<\/tr>\n
Column<\/td>\n	0 – 4<\/td>\n	210<\/td>\n<\/tr>\n
4 – 8<\/td>\n	210 \u2192 230<\/td>\n<\/tr>\n
8 – 18<\/td>\n	230 \u2192 260<\/td>\n<\/tr>\n
18 – 30<\/td>\n	260<\/td>\n<\/tr>\n
Injection port<\/td>\n	290<\/td>\n<\/tr>\n
Detector<\/td>\n	290<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Detection<\/em>\u00a0 Flame ionisation.<\/p>\n Injection<\/em>\u00a0 1 \u00b5L.<\/p>\n Relative retention<\/em>\u00a0 With reference to the second eluting peak of naftidrofuryl: impurity D = about 0.14; impurity B = about 0.55 (for the second eluting peak); impurity E = about 0.86; impurity F = about 1.04 (for the second eluting peak).<\/p>\n System suitability\u00a0<\/em> Test solution (b):<\/p>\n \u2014 resolution:<\/em> minimum 1.0 between the 2 peaks due to the diastereoisomers of naftidrofuryl.<\/p>\n Limits\u00a0 Test solution (a):<\/p>\n \u2014 impurity F: for the sum of the areas of the 2 peaks, maximum 0.20 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.20 per cent);<\/p>\n \u2014 impurity E: maximum 0.20 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.20 per cent);<\/p>\n \u2014 impurity D: maximum 0.10 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.10 per cent);<\/p>\n \u2014 any other impurity: for each impurity, maximum 0.10 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.10 per cent);<\/p>\n \u2014 total: maximum 0.50 per cent of the sum of the areas of the 2 peaks due to naftidroduryl (0.50 per cent);<\/p>\n \u2014 disregard limit: 0.02 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl (0.02 per cent); disregard any peaks due to impurity B.<\/p>\n Diastereoisomer ratio<\/p>\n Gas chromatography (2.2.28) as described in test B for related substances.<\/p>\n Limits\u00a0 Test solution (b):<\/p>\n \u2014 first eluting naftidrofuryl diastereoisomer: minimum 30 per cent of the sum of the areas of the 2 peaks due to naftidrofuryl.<\/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 0.350 g in 50 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20). \n1 mL of 0.1 M perchloric acid is equivalent to 47.36 mg of C26H35NO7.<\/p>\n IMPURITIES<\/h2>\n Specified impurities\u00a0 A, B, C, D, E, F.<\/p>\n $\"Naftidrofuryl$ <\/p>\n A. 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2-yl)propanoic acid,<\/p>\n $\"Naftidrofuryl$ <\/p>\n B. ethyl 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2-yl)propanoate,<\/p>\n $\"Naftidrofuryl$ <\/p>\n C. 2-(diethylamino)ethyl 3-(naphthalen-1-yl)-2-[(naphthalen-1-yl)methyl]propanoate,<\/p>\n $\"Naftidrofuryl$ <\/p>\n D. 2-(diethylamino)ethyl 3-[(2RS)-tetrahydrofuran-2-yl]propanoate,<\/p>\n $\"Naftidrofuryl$ <\/p>\n E. 2-(diethylamino)ethyl\u00a0 (2RS)-2-[(furan-2-yl)methyl]-3-(naphthalen-1-yl)propanoate,<\/p>\n $\"Naftidrofuryl$ <\/p>\n F. 2-(diethylamino)ethyl\u00a0 2-[(naphthalen-2-yl)methyl]-3-(tetrahydrofuran-2-yl)propanoate.<\/p>\n \n Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Vasodilator. Preparation Naftidrofuryl Capsules Ph Eur DEFINITION Mixture of 4 stereoisomers of 2-(diethylamino)ethyl 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2- yl)propanoate hydrogen oxalate. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white powder. Solubility Freely soluble in water, freely soluble or soluble in ethanol…<\/p>\n","protected":false},"author":5,"featured_media":25611,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-25610","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-volumes-1-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25610","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=25610"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25610\/revisions"}],"predecessor-version":[{"id":25652,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25610\/revisions\/25652"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25611"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25610"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25610"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25610"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

DEFINITION<\/h2>\nMixture of 4 stereoisomers of 2-(diethylamino)ethyl 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2- yl)propanoate hydrogen oxalate.<\/p>\nContent<\/strong><\/p>\n99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

TESTS<\/h2>\n

Absorbance (2.2.25)<\/h3>\nMaximum 0.1 at 430 nm.<\/p>\nDissolve 1.5 g in water R and dilute to 10 mL with the same solvent. If necessary use an ultrasonic bath.<\/p>\n

DEFINITION<\/h2>\n
Mixture of 4 stereoisomers of 2-(diethylamino)ethyl 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2- yl)propanoate hydrogen oxalate.<\/p>\n
Content<\/strong><\/p>\n
99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

Absorbance (2.2.25)<\/h3>\n
Maximum 0.1 at 430 nm.<\/p>\n
Dissolve 1.5 g in water R and dilute to 10 mL with the same solvent. If necessary use an ultrasonic bath.<\/p>\n