{"id":4841,"date":"2025-09-27T17:26:53","date_gmt":"2025-09-27T10:26:53","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=4841"},"modified":"2025-10-02T17:27:03","modified_gmt":"2025-10-02T10:27:03","slug":"bupivacaine","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/bupivacaine\/","title":{"rendered":"Bupivacaine"},"content":{"rendered":"

(Ph. Eur. monograph 2761)<\/p>\n

C_{18<\/sub>H_{28<\/sub>N_{2<\/sub>O\u00a0 \u00a0288.4\u00a0 \u00a038396-39-3<\/p>\n}}}

DEFINITION<\/h2>\n
(2RS)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide.<\/p>\n

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

CHARACTERS<\/h2>\n

Appearance<\/h3>\n
White or almost white, crystalline powder, crystals or granules.<\/p>\n

Solubility<\/h3>\n
Practically insoluble in water, freely soluble in ethanol (96 per cent), slightly soluble in heptane.<\/p>\n

IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: bupivacaine CRS.<\/p>\n

TESTS<\/h3>\n

Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and not more intensely coloured than reference solution BY7 (2.2.2, Method II).<\/p>\n
Dissolve 1.0 g in ethyl acetate R and dilute to 10 mL with the same solvent.<\/p>\n

Impurity F<\/h3>\n
Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n
Solvent mixture methanol R, water R (10:90 V\/V).<\/p>\n
Test solution: Dissolve 0.500 g of the substance to be examined in methanol R and dilute to 5.0 mL with the same solvent.<\/p>\n
Reference solution: Dissolve 25.0 mg of bupivacaine impurity F CRS in methanol R and dilute to 20.0 mL with the same solvent. Dilute 2.0 mL of the solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 100.0 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.05 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: end-capped ethylene-bridged octadecylsilyl silica gel for chromatography (hybrid material) R (3.5 \u03bcm).<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: methanol R2, 0.1 per cent V\/V solution of phosphoric acid R (10:90 V\/V);<\/p>\n
\u2014 mobile phase B: methanol R2;<\/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 – 10<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
10 – 15<\/td>\n 100 \u2192 5<\/td>\n 0 \u2192 95<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.5 mL\/min.<\/p>\n
Detection: Spectrophotometer at 210 nm.<\/p>\n
Injection: 5 \u03bcL.<\/p>\n
Retention time: Impurity F = about 2.5 min.<\/p>\n
System suitability: Reference solution:<\/p>\n
\u2014 signal-to-noise ratio: minimum 20 for the peak due to impurity F.<\/p>\n
Calculation of content:<\/p>\n
\u2014 use the concentration of impurity F in the reference solution.<\/p>\n
Limit:<\/p>\n
\u2014 impurity F: maximum 2.5 ppm.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Buffer solution 0.79 g\/L solution of ammonium hydrogen carbonate R adjusted to pH 8.3 with concentrated ammonia R.<\/p>\n
Test solution: Dissolve 80.0 mg of the substance to be examined in acetonitrile R and dilute to 100.0 mL with the same solvent.<\/p>\n
Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with acetonitrile R. Dilute 1.0 mL of this solution to 10.0 mL with the same solvent.<\/p>\n
Reference solution (b): Dissolve the contents of a vial of bupivacaine impurity D CRS in 1 mL of the test solution.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: end-capped extra-dense bonded octylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n
\u2014 temperature: 22 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: acetonitrile for chromatography R, buffer solution (10:90 V\/V);<\/p>\n
\u2014 mobile phase B: buffer solution, acetonitrile for chromatography R (10:90 V\/V);<\/p>\n\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 – 10<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
10 – 15<\/td>\n 100 \u2192 5<\/td>\n 0 \u2192 95<\/td>\n<\/tr>\n
<\/td>\n <\/td>\n <\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 225 nm.<\/p>\n
Autosampler: Set at 15 \u00b0C.<\/p>\n
Injection: 20 \u03bcL.<\/p>\n
Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity D.<\/p>\n
Relative retention: With reference to bupivacaine (retention time = about 24 min): impurity D = about 0.97.<\/p>\n
System suitability: Reference solution (b):<\/p>\n
\u2014 peak-to-valley ratio: minimum 1.5, where Hp = height above the baseline of the peak due to impurity D and
\nHv = height above the baseline of the lowest point of the curve separating this peak from the peak due to bupivacaine.<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of bupivacaine in reference solution (a).<\/p>\n
Limits:<\/p>\n
\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
Water (2.5.12)<\/h3>\n
Maximum 0.4 per cent, determined on 0.500 g.<\/p>\n
Sulfated ash (2.4.14)<\/h3>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/p>\n
Dissolve 0.220 g in 40 mL of glacial acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point
\npotentiometrically (2.2.20).<\/p>\n
1 mL of 0.1 M perchloric acid is equivalent to 28.84 mg of C18H28N2O.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities F.<\/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, C, D, E, G.<\/p>\n
$\"Bupivacaine\"$ <\/p>\n
A. N-(2,6-dimethylphenyl)pyridine-2-carboxamide,<\/p>\n
$\"Bupivacaine\"$ <\/p>\n
B. (2RS)-N-(2,6-dimethylphenyl)piperidine-2-carboxamide,<\/p>\n
$\"Bupivacaine\"$ <\/p>\n
C. 1-(2,6-dimethylphenyl)-1,5,6,7-tetrahydro-2H-azepin-2-one,<\/p>\n
$\"Bupivacaine\"$ <\/p>\n
D. (2RS)-2,6-dichloro-N-(2,6-dimethylphenyl)hexanamide,<\/p>\n
$\"Bupivacaine\"$ <\/p>\n
E. 6-(butylamino)-N-(2,6-dimethylphenyl)hexanamide,<\/p>\n
$\"Bupivacaine\"$ <\/p>\n
F. 2,6-dimethylaniline,<\/p>\n
$\"Bupivacaine\"$ <\/p>\n
G. (2RS)-1-butyl-N-(2,4-dimethylphenyl)piperidine-2-carboxamide.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 2761) C18H28N2O\u00a0 \u00a0288.4\u00a0 \u00a038396-39-3 DEFINITION (2RS)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide. Content 99.0 per cent to 101.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, crystalline powder, crystals or granules. Solubility Practically insoluble in water, freely soluble in ethanol (96 per cent), slightly soluble in heptane. IDENTIFICATION Infrared absorption spectrophotometry (2.2.24). Comparison: bupivacaine CRS. TESTS…<\/p>\n","protected":false},"author":4,"featured_media":4858,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-4841","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\/4841","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=4841"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/4841\/revisions"}],"predecessor-version":[{"id":5835,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/4841\/revisions\/5835"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/4858"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=4841"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=4841"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=4841"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

DEFINITION<\/h2>\n(2RS)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide.<\/p>\n

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

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or almost white, crystalline powder, crystals or granules.<\/p>\n

Solubility<\/h3>\nPractically insoluble in water, freely soluble in ethanol (96 per cent), slightly soluble in heptane.<\/p>\n

IDENTIFICATION<\/h2>\nInfrared absorption spectrophotometry (2.2.24).<\/p>\nComparison: bupivacaine CRS.<\/p>\n