{"id":25232,"date":"2025-11-04T10:26:36","date_gmt":"2025-11-04T03:26:36","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=25232"},"modified":"2025-11-04T11:24:52","modified_gmt":"2025-11-04T04:24:52","slug":"nicotine","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/nicotine\/","title":{"rendered":"Nicotine"},"content":{"rendered":"

(Ph. Eur. monograph 1452)<\/p>\n

C_{10<\/sub>H_{14<\/sub>N_{2\u00a0<\/sub> \u00a0 \u00a0 \u00a0 \u00a0 \u00a0162.2\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a054-11-5<\/p>\n}}}

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

Aid to smoking cessation.<\/p>\n

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

Nicotine Inhalation Cartridges<\/p>\n

Nicotine Nasal Spray<\/p>\n

Nicotine Sublingual Tablets<\/p>\n

Nicotine Transdermal Patches<\/p>\n

DEFINITION<\/h2>\n
3-[(2S)-1-Methylpyrrolidin-2-yl]pyridine.<\/p>\n
Content<\/h3>\n
99.0 per cent to 101.0 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Colourless or brownish viscous liquid, volatile, hygroscopic.<\/p>\n
Solubility<\/h3>\n
Soluble in water, miscible with anhydrous ethanol.<\/p>\n
IDENTIFICATION<\/h2>\n
A. Specific optical rotation (see Tests).<\/p>\n
B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: Ph. Eur. reference spectrum of nicotine.<\/p>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
Dissolve 1.0 g in water R and dilute to 10 mL with the same solvent. The solution is clear (2.2.1) and not more intensely coloured than reference solution Y5, BY5 or R5
\n(2.2.2, Method II).<\/p>\n
Specific optical rotation (2.2.7)<\/h4>\n
-140 to -152.<\/p>\n
Dissolve 1.00 g in anhydrous ethanol R and dilute to 50.0 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n
Test solution: Dissolve 20.0 mg of the substance to be examined in water R and dilute to 25.0 mL with the same solvent.<\/p>\n
Reference solution (a): Dissolve the contents of a vial of nicotine for system suitability CRS (containing impurities A, B, C, D, E, F and G) in 1.0 mL of water R.<\/p>\n
Reference solution (b): Dilute 1.0 mL of the test solution to 10.0 mL with water R. Dilute 1.0 mL of this solution to 100.0 mL with water R.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: end-capped polar-embedded octadecylsilyl amorphous organosilica polymer R (5 \u03bcm).<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: to 900 mL of water R, add 25 mL of a 60 g\/L solution of acetic acid R, then add 6 mL of concentrated ammonia R1. Adjust to pH 10.0 with dilute ammonia R2 or dilute acetic acid R and dilute to 1000 mL with water R;<\/p>\n
\u2014 mobile phase B: acetonitrile R;<\/p>\n\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 – 3<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
3 – 3.01<\/td>\n 100 \u2192 95<\/td>\n 0 \u2192 5<\/td>\n<\/tr>\n
3.01 – 28<\/td>\n 95 \u2192 74<\/td>\n 5 \u2192 26<\/td>\n<\/tr>\n
28 – 32<\/td>\n 74 \u2192 60<\/td>\n 26 \u2192 40<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 254 nm.<\/p>\n
Injection: 20 \u03bcL.<\/p>\n
Identification of impurities: Use the chromatogram supplied with nicotine for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities A, B, C, D, E, F and G.<\/p>\n
Relative retention: With reference to nicotine (retention time = about 17.8 min): impurity E = about 0.3; impurity C = about 0.55; impurity F = about 0.7; impurity A = about 0.8; impurity D = about 0.86; impurity G = about 0.9; impurity B = about 1.6.
\nSystem suitability Reference solution (a):<\/p>\n
\u2014 resolution: minimum 2.5 between the peaks due to impurity G and nicotine.<\/p>\n
Limits:<\/p>\n
\u2014 impurities A, B, C, D, E, F, G: for each impurity, not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);<\/p>\n
\u2014 unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.10 per cent);<\/p>\n
\u2014 total: not more than 8 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.8 per cent);<\/p>\n
\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n
Water (2.5.12)<\/h4>\n
Maximum 0.5 per cent, determined on 1.00 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 60.0 mg in 30 mL of anhydrous acetic acid R. 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 8.11 mg of C_{10<\/sub>H_{14<\/sub>N_{2<\/sub>.<\/p>\n}}}
STORAGE<\/h2>\n
Under nitrogen, in an airtight container, protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities A, B, C, D, E, F, G.<\/p>\n
$\"Nicotine\"$ <\/p>\n
A. (2S)-1,2,3,6-tetrahydro-2,3\u2032-bipyridyl (anatabine),<\/p>\n
$\"Nicotine\"$ <\/p>\n
B. 3-(1-methyl-1H-pyrrol-2-yl)pyridine (\u03b2-nicotyrine),<\/p>\n
$\"Nicotine\"$ <\/p>\n
C. (5S)-1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one (cotinine),<\/p>\n
$\"Nicotine\"$ <\/p>\n
D. 3-(4,5-dihydro-3H-pyrrol-2-yl)pyridine (myosmine),<\/p>\n
$\"Nicotine\"$ <\/p>\n
E. (1RS,2S)-1-methyl-2-(pyridin-3-yl)pyrrolidine 1-oxide (nicotine N\u2032-oxide),<\/p>\n
$\"Nicotine\"$ <\/p>\n
F. 3-[(2S)-pyrrolidin-2-yl]pyridine (nornicotine),<\/p>\n
$\"Nicotine\"$ <\/p>\n
G. 3-[(2S)-piperidin-2-yl]pyridine (anabasine).<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 1452) C10H14N2\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0162.2\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a054-11-5 Action and use Aid to smoking cessation. Preparations Nicotine Inhalation Cartridges Nicotine Nasal Spray Nicotine Sublingual Tablets Nicotine Transdermal Patches DEFINITION 3-[(2S)-1-Methylpyrrolidin-2-yl]pyridine. Content 99.0 per cent to 101.0 per cent (anhydrous substance). CHARACTERS Appearance Colourless or brownish viscous liquid,…<\/p>\n","protected":false},"author":2,"featured_media":25256,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25232","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\/25232","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=25232"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25232\/revisions"}],"predecessor-version":[{"id":25262,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25232\/revisions\/25262"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25256"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25232"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25232"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25232"}],"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 – 3<\/td>\n	100<\/td>\n	0<\/td>\n<\/tr>\n
3 – 3.01<\/td>\n	100 \u2192 95<\/td>\n	0 \u2192 5<\/td>\n<\/tr>\n
3.01 – 28<\/td>\n	95 \u2192 74<\/td>\n	5 \u2192 26<\/td>\n<\/tr>\n
28 – 32<\/td>\n	74 \u2192 60<\/td>\n	26 \u2192 40<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 1.0 mL\/min.<\/p>\n Detection: Spectrophotometer at 254 nm.<\/p>\n Injection: 20 \u03bcL.<\/p>\n Identification of impurities: Use the chromatogram supplied with nicotine for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities A, B, C, D, E, F and G.<\/p>\n Relative retention: With reference to nicotine (retention time = about 17.8 min): impurity E = about 0.3; impurity C = about 0.55; impurity F = about 0.7; impurity A = about 0.8; impurity D = about 0.86; impurity G = about 0.9; impurity B = about 1.6. \nSystem suitability Reference solution (a):<\/p>\n \u2014 resolution: minimum 2.5 between the peaks due to impurity G and nicotine.<\/p>\n Limits:<\/p>\n \u2014 impurities A, B, C, D, E, F, G: for each impurity, not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);<\/p>\n \u2014 unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.10 per cent);<\/p>\n \u2014 total: not more than 8 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.8 per cent);<\/p>\n \u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n Water (2.5.12)<\/h4>\n Maximum 0.5 per cent, determined on 1.00 g.<\/p>\n ASSAY<\/h2>\n Dissolve 60.0 mg in 30 mL of anhydrous acetic acid R. 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 8.11 mg of C_{10<\/sub>H_{14<\/sub>N_{2<\/sub>.<\/p>\n}}} STORAGE<\/h2>\n Under nitrogen, in an airtight container, protected from light.<\/p>\n IMPURITIES<\/h2>\n Specified impurities A, B, C, D, E, F, G.<\/p>\n $\"Nicotine\"$ <\/p>\n A. (2S)-1,2,3,6-tetrahydro-2,3\u2032-bipyridyl (anatabine),<\/p>\n $\"Nicotine\"$ <\/p>\n B. 3-(1-methyl-1H-pyrrol-2-yl)pyridine (\u03b2-nicotyrine),<\/p>\n $\"Nicotine\"$ <\/p>\n C. (5S)-1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one (cotinine),<\/p>\n $\"Nicotine\"$ <\/p>\n D. 3-(4,5-dihydro-3H-pyrrol-2-yl)pyridine (myosmine),<\/p>\n $\"Nicotine\"$ <\/p>\n E. (1RS,2S)-1-methyl-2-(pyridin-3-yl)pyrrolidine 1-oxide (nicotine N\u2032-oxide),<\/p>\n $\"Nicotine\"$ <\/p>\n F. 3-[(2S)-pyrrolidin-2-yl]pyridine (nornicotine),<\/p>\n $\"Nicotine\"$ <\/p>\n G. 3-[(2S)-piperidin-2-yl]pyridine (anabasine).<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 1452) C10H14N2\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0162.2\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a054-11-5 Action and use Aid to smoking cessation. Preparations Nicotine Inhalation Cartridges Nicotine Nasal Spray Nicotine Sublingual Tablets Nicotine Transdermal Patches DEFINITION 3-[(2S)-1-Methylpyrrolidin-2-yl]pyridine. Content 99.0 per cent to 101.0 per cent (anhydrous substance). CHARACTERS Appearance Colourless or brownish viscous liquid,…<\/p>\n","protected":false},"author":2,"featured_media":25256,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25232","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\/25232","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=25232"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25232\/revisions"}],"predecessor-version":[{"id":25262,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25232\/revisions\/25262"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25256"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25232"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25232"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25232"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

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

CHARACTERS<\/h2>\n

Appearance<\/h3>\nColourless or brownish viscous liquid, volatile, hygroscopic.<\/p>\n

Solubility<\/h3>\nSoluble in water, miscible with anhydrous ethanol.<\/p>\n

IDENTIFICATION<\/h2>\nA. Specific optical rotation (see Tests).<\/p>\nB. Infrared absorption spectrophotometry (2.2.24).<\/p>\nComparison: Ph. Eur. reference spectrum of nicotine.<\/p>\n

TESTS<\/h2>\n

Appearance of solution<\/h3>\nDissolve 1.0 g in water R and dilute to 10 mL with the same solvent. The solution is clear (2.2.1) and not more intensely coloured than reference solution Y5, BY5 or R5\n(2.2.2, Method II).<\/p>\n

Specific optical rotation (2.2.7)<\/h4>\n-140 to -152.<\/p>\nDissolve 1.00 g in anhydrous ethanol R and dilute to 50.0 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\nMaximum 0.5 per cent, determined on 1.00 g.<\/p>\n

ASSAY<\/h2>\nDissolve 60.0 mg in 30 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid determining the end-point potentiometrically (2.2.20).<\/p>\n1 mL of 0.1 M perchloric acid is equivalent to 8.11 mg of C10<\/sub>H14<\/sub>N2<\/sub>.<\/p>\n

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

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

Appearance<\/h3>\n
Colourless or brownish viscous liquid, volatile, hygroscopic.<\/p>\n

Solubility<\/h3>\n
Soluble in water, miscible with anhydrous ethanol.<\/p>\n

IDENTIFICATION<\/h2>\n
A. Specific optical rotation (see Tests).<\/p>\n
B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: Ph. Eur. reference spectrum of nicotine.<\/p>\n

Appearance of solution<\/h3>\n
Dissolve 1.0 g in water R and dilute to 10 mL with the same solvent. The solution is clear (2.2.1) and not more intensely coloured than reference solution Y5, BY5 or R5
\n(2.2.2, Method II).<\/p>\n

Specific optical rotation (2.2.7)<\/h4>\n
-140 to -152.<\/p>\n
Dissolve 1.00 g in anhydrous ethanol R and dilute to 50.0 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\n
Maximum 0.5 per cent, determined on 1.00 g.<\/p>\n

ASSAY<\/h2>\n
Dissolve 60.0 mg in 30 mL of anhydrous acetic acid R. 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 8.11 mg of C_{10<\/sub>H_{14<\/sub>N_{2<\/sub>.<\/p>\n}}}

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