{"id":5440,"date":"2025-09-29T14:15:36","date_gmt":"2025-09-29T07:15:36","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=5440"},"modified":"2025-10-04T16:28:37","modified_gmt":"2025-10-04T09:28:37","slug":"brivaracetam-injection-or-infusion","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/brivaracetam-injection-or-infusion\/","title":{"rendered":"Brivaracetam Injection or Infusion"},"content":{"rendered":"

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

General Notices<\/p>\n

(Ph. Eur. monograph 3142)<\/em><\/p>\n

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

Anticonvulsant; synaptic vesicle protein 2A (SV2A) ligand; adjunctive therapy of partial-onset seizures.<\/p>\n

Ph Eur<\/p>\n

DEFINITION<\/h2>\n
Sterile solution for injection or infusion of Brivaracetam (3139), for human use.<\/p>\n
It complies with the monograph Parenteral preparations (0520) and the following additional requirements.<\/em><\/p>\n
Content<\/strong><\/p>\n
95.0 per cent to 105.0 per cent of the content of brivaracetam (C_{11<\/sub>H_{20<\/sub>N_{2<\/sub>O_{2<\/sub>) stated on the label.<\/p>\n}}}}
IDENTIFICATION<\/h2>\n
A. Examine the chromatograms obtained in the assay.<\/p>\n
Results<\/em> The principal peak in the chromatogram obtained with the test solution is similar in retention time and size to the principal peak in the chromatogram obtained with reference solution (f).<\/p>\n
B. Thin-layer chromatography (2.2.27).<\/p>\n
Test solution<\/em> The preparation to be examined.<\/p>\n
Reference solution<\/em> Dissolve 10 mg of brivaracetam CRS in 1 mL of methylene chloride R.<\/p>\n
Plate<\/em> TLC silica gel F254 plate R (5-40 \u03bcm) [or TLC silica gel F254 plate R (2-10 \u03bcm)].<\/p>\n
Mobile phase<\/em> concentrated ammonia R, methanol R, ethyl acetate R (3:12:85 V\/V\/V).<\/p>\n
Application<\/em> 20 \u03bcL, as bands of 10 mm.<\/p>\n
Development<\/em> Over 1\/2 of the plate.<\/p>\n
Drying<\/em> In air for 1-2 min.<\/p>\n
Detection<\/em> Expose to iodine vapour until the spots appear and examine in daylight.<\/p>\n
Results<\/em> The spot in the chromatogram obtained with the test solution is similar in position to the spot in the chromatogram obtained with the reference solution.<\/p>\n
TESTS<\/h2>\n
Related substances<\/strong><\/p>\n
Liquid chromatography (2.2.29).<\/p>\n
Test solution<\/em> Dilute a suitable volume of the preparation to be examined with water R to obtain a concentration of brivaracetam of 0.50 mg\/mL.<\/p>\n
Reference solution (a)<\/em> Dilute 1.0 mL of the test solution to 100.0 mL with water R. Dilute 2.0 mL of this solution to 10.0 mL with water R.<\/p>\n
Reference solution (b)<\/em> Dissolve 3 mg of brivaracetam R and 3 mg of brivaracetam impurity A CRS in water R and dilute to 5 mL with the same solvent.<\/p>\n
Reference solution (c)<\/em> Dissolve 5 mg of brivaracetam impurity D CRS and 5 mg of brivaracetam impurity E CRS in water R and dilute to 100 mL with the same solvent. Dilute 1 mL of this solution to 50 mL with water R.<\/p>\n
Reference solution (d)<\/em> Dissolve 65.0 mg of brivaracetam CRS in water R and dilute to 100.0 mL with the same solvent.<\/p>\n
Reference solutions (e), (f), (g), (h)<\/em> Dilute reference solution (d) with water R as necessary to obtain reference solutions with a concentration of 0.58 mg\/mL, 0.50 mg\/mL (reference solution (f)), 0.43 mg\/mL and 0.35 mg\/mL.
\nA precolumn containing end-capped ethylene-bridged octadecylsilyl silica gel for chromatography (hybrid material) R (1.7 \u03bcm) may be used.<\/p>\n
Column<\/em>:<\/p>\n
\u2014 size<\/em>: l = 0.10 m, \u00d8 = 2.1 mm;<\/p>\n
\u2014 temperature<\/em>: 38 \u00b0C;<\/p>\n
\u2014 stationary phase<\/em>: end-capped ethylene-bridged octadecylsilyl silica gel for chromatography (hybrid material) R
\n(1.7 \u03bcm).<\/p>\n
Mobile phase<\/em>:<\/p>\n
\u2014 mobile phase A<\/em>: formic acid R, water for chromatography R (0.1:1000 V\/V);<\/p>\n
\u2014 mobile phase B<\/em>: formic acid R, acetonitrile R1 (0.1:1000 V\/V);<\/p>\n\n\n\n\n\n\n\n
Time
\n(min)<\/td>\n Mobile phase A
\n(per cent V\/V)<\/td>\n Mobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 1<\/td>\n 92<\/td>\n 8<\/td>\n<\/tr>\n
1 – 12<\/td>\n 92 \u2192 72<\/td>\n 8 \u2192 28<\/td>\n<\/tr>\n
12 – 12.5<\/td>\n 72 \u2192 50<\/td>\n 28 \u219250<\/td>\n<\/tr>\n
12.5 – 13.5<\/td>\n 50<\/td>\n 50<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate<\/em> 0.5 mL\/min.<\/p>\n
Detection<\/em> Spectrophotometer at 205 nm.<\/p>\n
Injection<\/em> 3 \u03bcL of the test solution and reference solutions (a), (b) and (c).<\/p>\n
Identification of impurities<\/em> Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity A; use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities D and E.<\/p>\n
Relative retention<\/em> With reference to brivaracetam (retention time = about 8 min): impurity A = about 1.04;
\nimpurity D = about 1.2; impurity E = about 1.3.<\/p>\n
System suitability<\/em> Reference solution (b):<\/p>\n
\u2014 resolution: minimum 2.0 between the peaks due to brivaracetam and impurity A.<\/p>\n
Calculation of percentage contents<\/em>:<\/p>\n
\u2014 for each impurity, use the concentration of brivaracetam in reference solution (a).<\/p>\n
Limits<\/em>:<\/p>\n
\u2014 sum of impurities D and E: maximum 0.50 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.20 per cent;<\/p>\n
\u2014 total: maximum 0.80 per cent;<\/p>\n
\u2014 reporting threshold: 0.10 per cent; disregard the peak due to impurity A.<\/p>\n
ASSAY<\/h2>\n
Liquid chromatography (2.2.29) as described in the test for related substances, with the following modifications.<\/p>\n
Injection<\/em> Test solution and reference solutions (d), (e), (f), (g) and (h).<\/p>\n
System suitability<\/em>:<\/p>\n
\u2014 repeatability: maximum relative standard deviation of 1.0 per cent determined on 6 injections of reference solution (f);<\/p>\n
\u2014 the coefficient of determination (r ) calculated for the calibration curve is not less than 0.995.<\/p>\n
Calculate the percentage content of C_{11<\/sub>H_{20<\/sub>N_{2<\/sub>O_{2<\/sub> using the calibration curve and taking into account the assigned content of brivaracetam CRS.<\/p>\n}}}}
IMPURITIES<\/h2>\n
Specified impurities<\/em> D, E.<\/p>\n
Other detectable impurities<\/em> (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph): A.<\/p>\n
$\"\"$
\nA. (2S)-2-[(4S)-2-oxo-4-propylpyrrolidin-1-yl]butanamide,<\/p>\n
$\"\"$ D. (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanoic acid,<\/p>\n
$\"\"$ <\/p>\n
E. (2S)-2-[(4S)-2-oxo-4-propylpyrrolidin-1-yl]butanoic acid.<\/p>\n
Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":"
Edition: BP 2025 (Ph. Eur. 11.6 update) General Notices (Ph. Eur. monograph 3142) Action and use Anticonvulsant; synaptic vesicle protein 2A (SV2A) ligand; adjunctive therapy of partial-onset seizures. Ph Eur DEFINITION Sterile solution for injection or infusion of Brivaracetam (3139), for human use. It complies with the monograph Parenteral preparations (0520) and the following additional…<\/p>\n","protected":false},"author":5,"featured_media":5489,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-5440","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-formulated-preparations-specific-monographs"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/5440","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=5440"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/5440\/revisions"}],"predecessor-version":[{"id":9184,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/5440\/revisions\/9184"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/5489"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=5440"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=5440"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=5440"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time \n(min)<\/td>\n	Mobile phase A \n(per cent V\/V)<\/td>\n	Mobile phase B \n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 1<\/td>\n	92<\/td>\n	8<\/td>\n<\/tr>\n
1 – 12<\/td>\n	92 \u2192 72<\/td>\n	8 \u2192 28<\/td>\n<\/tr>\n
12 – 12.5<\/td>\n	72 \u2192 50<\/td>\n	28 \u219250<\/td>\n<\/tr>\n
12.5 – 13.5<\/td>\n	50<\/td>\n	50<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate<\/em> 0.5 mL\/min.<\/p>\n Detection<\/em> Spectrophotometer at 205 nm.<\/p>\n Injection<\/em> 3 \u03bcL of the test solution and reference solutions (a), (b) and (c).<\/p>\n Identification of impurities<\/em> Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity A; use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities D and E.<\/p>\n Relative retention<\/em> With reference to brivaracetam (retention time = about 8 min): impurity A = about 1.04; \nimpurity D = about 1.2; impurity E = about 1.3.<\/p>\n System suitability<\/em> Reference solution (b):<\/p>\n \u2014 resolution: minimum 2.0 between the peaks due to brivaracetam and impurity A.<\/p>\n Calculation of percentage contents<\/em>:<\/p>\n \u2014 for each impurity, use the concentration of brivaracetam in reference solution (a).<\/p>\n Limits<\/em>:<\/p>\n \u2014 sum of impurities D and E: maximum 0.50 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.20 per cent;<\/p>\n \u2014 total: maximum 0.80 per cent;<\/p>\n \u2014 reporting threshold: 0.10 per cent; disregard the peak due to impurity A.<\/p>\n ASSAY<\/h2>\n Liquid chromatography (2.2.29) as described in the test for related substances, with the following modifications.<\/p>\n Injection<\/em> Test solution and reference solutions (d), (e), (f), (g) and (h).<\/p>\n System suitability<\/em>:<\/p>\n \u2014 repeatability: maximum relative standard deviation of 1.0 per cent determined on 6 injections of reference solution (f);<\/p>\n \u2014 the coefficient of determination (r ) calculated for the calibration curve is not less than 0.995.<\/p>\n Calculate the percentage content of C_{11<\/sub>H_{20<\/sub>N_{2<\/sub>O_{2<\/sub> using the calibration curve and taking into account the assigned content of brivaracetam CRS.<\/p>\n}}}} IMPURITIES<\/h2>\n Specified impurities<\/em> D, E.<\/p>\n Other detectable impurities<\/em> (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph): A.<\/p>\n $\"\"$ \nA. (2S)-2-[(4S)-2-oxo-4-propylpyrrolidin-1-yl]butanamide,<\/p>\n $\"\"$ D. (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanoic acid,<\/p>\n $\"\"$ <\/p>\n E. (2S)-2-[(4S)-2-oxo-4-propylpyrrolidin-1-yl]butanoic acid.<\/p>\n Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) General Notices (Ph. Eur. monograph 3142) Action and use Anticonvulsant; synaptic vesicle protein 2A (SV2A) ligand; adjunctive therapy of partial-onset seizures. Ph Eur DEFINITION Sterile solution for injection or infusion of Brivaracetam (3139), for human use. It complies with the monograph Parenteral preparations (0520) and the following additional…<\/p>\n","protected":false},"author":5,"featured_media":5489,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-5440","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-formulated-preparations-specific-monographs"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/5440","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=5440"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/5440\/revisions"}],"predecessor-version":[{"id":9184,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/5440\/revisions\/9184"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/5489"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=5440"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=5440"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=5440"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}