pointerEUROPEAN PHARMACOPOEIA 5.4Rocuronium
bromide
04/2006:1764ROCURONIUM BROMIDE Rocuronii
bromidum C 32H 53BrN 2O 4M r 610DEFINITION 1-[17β-(Acetyloxy)-3α-hydroxy-2β-(morpholin-4-yl)-5α-
androstan-16β-yl]-1-(prop-2-enyl)pyrrolidinium bromide.Content :99.0per cent to 101.0per cent (anhydrous substance).CHARACTERS Appearance :almost white or pale yellow,slightly hygroscopic powder.Solubility :freely soluble in water and in anhydrous ethanol.IDENTIFICATION A.Infrared absorption spectrophotometry (2.2.24).Comparison :ference spectrum of rocuronium bromide .B.Solution S (e Tests)gives reaction (a)of bromides (2.3.1).TESTS Solution S .Dissolve 0.10g in carbon dioxide-free water R and dilute to 10ml with the same solvent.Appearance of solution .Solution S is
clear (2.2.1)and not more intenly coloured than reference solution BY 5(2.2.2,Method II ).Specific optical rotation (2.2.7):+28.5to +32.0(anhydrous substance).Dissolve 0.250g in a 5.15g/l solution of hydrochloric acid R and dilute to 25.0ml with the same solution.pH (2.2.3):8.9to 9.5for solution S.Related substances .Liquid chromatography (2.2.29).Solvent mixture :water R ,acetonitrile R1(10:90V/V ).Test solution
.Dissolve 0.100g of the substance to be examined in the solvent mixture and dilute to 10.0ml with th
e solvent mixture.Reference solution (a).Dilute 1.0ml of the test solution to 100.0ml with the solvent mixture.Dilute 1.0ml of this solution to 10.0ml with the mobile pha.Reference solution (b).Dissolve 5mg of rocuronium for peak identification CRS (containing impurities A,B,C,F,G and H)in the solvent mixture and dilute to 5ml with the solvent mixture.Column :—size :l =0.25m,Ø=4.6mm,—stationary pha :silica gel for chromatography R (5µm),—temperature :30°C.Mobile
pha :mix 100volumes of a
4.53
地点英语g/l solution李阳
of
tetramethylammonium hydroxide R adjusted to pH 7.4with
phosphoric acid R and 900volumes of acetonitrile R1.Flow rate :2.0ml/min.
Detection :spectrophotometer at 210nm.
Injection :5µl of the test solution,reference solutions (a)
and (b)and the solvent mixture (blank).Run time :2.5times the retention time of rocuronium.
Relative retention with reference to
rocuronium (retention time =about 9min):impurity A =about 0.20;
impurity G =about 0.44;impurity F =about 0.75;
impurity B =about 0.80;impurity D =about 0.90;impurity H =about 0.95;impurity C =about 1.20;
impurity E =about 1.53.System suitability :reference solution (b):
—the chromatogram obtained is similar to the chromatogram supplied with rocuronium for peak identification CRS .Limits :
—correction
factors :for the calculation of content,multiply the peak areas of the following impurities by the corresponding correction factor:impurity A =0.47;impurity F =1.26;impurity G =0.43;impurity H =0.35;—impurity A :not more than twice the area of the principal
peak in the chromatogram obtained with reference
solution (a)(0.2per cent);—impurities B,C
:for each impurity,not more than 3times
the area of the principal peak in the chromatogram obtained with reference solution (a)(0.3per cent);
—impurities D,E,F,G,H :for each impurity,not more
than the area of the principal peak in the chromatogram obtained with reference solution (a)(0.1per cent);
—unspecified impurities :for each impurity,not more than
the area of the principal peak in the chromatogram obtained with reference solution (a)(0.1per cent);—total :not more than 15times the area of the principal
peak in the chromatogram obtained with reference
solution (a)(1.5per cent);—disregard limit :0.5times the area of the principal peak in the chromatogra
m obtained with reference solution (a)
(0.05
per cent);disregard the peaks due to the blank and to bromide ion eluting just before impurity A.
Chlorides .Liquid chromatography (2.2.29).
Test solution .Dissolve 20.0mgquarterback
of the substance to be examined in water R and dilute to 20.0ml with the same solvent.
Reference solution (a).Dissolve 0.824g
of sodium
chloride R and 0.644g of sodium bromide R in water R and
dilute to 1000.0ml with the same solvent.Dilute 1.0ml of this solution to 50.0ml with water R .
Reference solution (b).Dissolve 0.824g of sodium chloride R in water
R
and dilute to 1000.0
ml
charterparty
with the same
典身solvent.Dilute 5.0ml of the solution to 50.0ml with water R .
Dilute 2.0ml of this solution to 50.0ml with water R .Blank solution .Water R .
Precolumn :
—size :l =0.05m,Ø=
4.0mm,
bbc可可英语
—stationary pha :anion exchange resin R (13µm).
Column :
—size :l =0.25m,Ø=4.0mm,
—stationary
pha :anion exchange resin R (13µm).
Mobile pha :a solution containing 0.063g/l of sodium
hydrogen carbonate R and 0.212g/l of anhydrous sodium carbonate R .General Notices (1)apply to all monographs and other texts 4013
Rocuronium bromide EUROPEAN PHARMACOPOEIA
5.4Flow rate :2.0ml/min.Detection :conductivity detector t at 100µS/V and
maintained at 30°C.U a lf-generating anion suppressor.
Injection :25µl.
Retention times :chloride =about 1.7min;
bromide =about 2.8min.System suitability :reference solution (a):
—resolution :minimum 2.5between the peaks due to
chloride and bromide.Limit :—chlorides :not more than 0.5times the area of the
principal peak in the chromatogram obtained with reference solution (b)(0.1per cent).Heavy metals (2.4.8):maximum 10ppm.2.0g complies with test C.Prepare the reference solution using 2ml of lead standard solution (10ppm Pb)R .Water (2.5.12):maximum 4.0per cent,determined on
0.400g.Sulphated ash (2.4.14):maximum 0.1per cent,determined
on 1.0g.ASSAY
Dissolve 0.400g in 40ml of glacial acetic acid R .Titrate
with 0.1M perchloric acid ,determining the end-point
potentiometrically (2.2.20).1ml of 0.1M perchloric acid is equivalent to 60.97mg
of C 32H 53BrN 2O 4
.STORAGE In an airtight container,protected from light.IMPURITIES Specified impurities:A,B,C,D,E,F,G,H
.
A.R =CO-CH 3:3α-hydroxy-2β-(morpholin-4-yl)-16β-(pyrrolidin-1-yl)-5α-androstan-17β-yl acetate,G.R
=H:2β-(morpholin-4-yl)-16β-(pyrrolidin-1-yl)-5α-androstane-3α,17β
-diol,B.R
深圳瑜伽教练培训学校=R ′=CO-CH 3:1-[3α,17β-bis(acetyloxy)-2β-(morpholin-4-yl)-5α-androstan-16β-yl]-1-(prop-2-enyl)pyrrolidinium,C.R
=R ′=H:1-[3α,17β-dihydroxy-2β-(morpholin-4-yl)-5α-androstan-16β-yl]-1-(prop-2-enyl)pyrrolidinium,D.R
=CO-CH 3,R ′=H:1-[3α-(acetyloxy)-17β
单程票英语
-hydroxy-2β-(morpholin-4-yl)-5α-androstan-16β-yl]-1-(prop-2-短裙的英语单词
enyl)pyrrolidinium,E.R =H:1-[17β-(acetyloxy)-3α-hydroxy-2β-(pyrrolidin-1-yl)-5α-androstan-16β-yl]-1-(prop-2-enyl)pyrrolidinium,F.R
=CO-CH 3:1-[3α,17β-bis(acetyloxy)-2β-(pyrrolidin-1-yl)-5α-androstan-16β
-yl]-1-(prop-2-enyl)pyrrolidinium,H.1-[17β-(acetyloxy)-2-(morpholin-4-yl)-3-oxo-5α-androst-1-en-16β-yl]-1-(prop-2-enyl)pyrrolidinium.4014See the information ction on general monographs (cover pages)
