Enoxaparin sodium EUROPEAN PHARMACOPOEIA7.0
Relative retention with reference to enilconazole(retention
time=about10min):impurity A=about0.6;impurity B=about
0.7;impurity C=about0.8;impurity D=about0.9;
impurity E=about1.03;impurity F=about1.1.
System suitability:reference solution(a):
—resolution:minimum2.5between the peaks due to
理发
enilconazole and impurity E.
Limits:
—impurities A,B,C,D,E,F:for each impurity,not more than
twice the area of the principal peak in the chromatogram
obtained with reference solution(b)(1.0per cent),and not
more than1such peak has an area greater than the area
of the principal peak in the chromatogram obtained with
reference solution(b)(0.5per cent);
—unspecified impurities:for each impurity,not more than
0.4times the area of the principal peak in the chromatogram
obtained with reference solution(b)(0.20per cent);
—total:not more than4times the area of the principal peak
in the chromatogram obtained with reference solution(b)
(2.0per cent);
—disregard limit:0.1times the area of the principal peak
in the chromatogram obtained with reference solution(b)
(0.05per cent).
Loss on drying(2.2.32):maximum0.5per cent,determined on
1.000g by drying in vacuo at40°C for4h.
Sulfated ash(2.4.14):maximum0.1per cent,determined on
1.0g.
ASSAY
Dissolve0.230g in50mL of a mixture of1volume of anhydrous
acetic acid R and7volumes of methyl ethyl ketone R.Titrate
with0.1M perchloric acid using0.2mL of naphtholbenzein
solution R as indicator.
1mL of0.1M perchloric acid is equivalent to29.72mg of
C
14
H
14
八公山风景区Cl
2
N
2
O.
STORAGE
In an airtight container,protected from light.
IMPURITIES
Specified impurities:A,B,C,D,E,F.
A.R1=R2=H:(2RS)-2-(2,4-dichlorophenyl)-2-(prop-2-
enyloxy)ethanamine,
B.R1=H,R2=CH
2
-CH=CH
2
:N-[(2RS)-2-(2,4-dichlorophenyl)-
2-(prop-2-enyloxy)ethyl]prop-2-en-1-amine,
C.R1=CHO,R2=H:N-[(2RS)-2-(2,4-dichlorophenyl)-2-(prop-
2-enyloxy)ethyl]formamide,
D.R1=CHO,R2=CH
2
-CH=CH
2
:N-[(2RS)-2-(2,4-
dichlorophenyl)-2-(prop-2-enyloxy)ethyl]-N-(prop-2-
enyl)formamide,
E.(1RS)-1-(2,4-dichlorophenyl)-2-(-1H-imidazol-1-yl)ethanol,
F.1-[(2RS)-2-(3,4-dichlorophenyl)-2-(prop-2-enyloxy)ethyl]-1H-
imidazole.
01/2008:1097
ENOXAPARIN SODIUM
Enoxaparinum natricum
蜜汁叉烧肉
DEFINITION
Enoxaparin sodium is the sodium salt of a low-molecular-mass
heparin that is obtained by alkaline depolymerisation
of the benzyl ester derivative of heparin from porcine
intestinal mucosa.Enoxaparin consists of a complex t
of oligosaccharides that have not yet been completely
characterid.Bad on current knowledge,the majority of the
广目天components have a4-enopyrano uronate structure at the
non-reducing end of their chain.15per cent to25per cent of
the components have a1,6-anhydro structure at the reducing
end of their chain.
Enoxaparin sodium complies with the monograph
Low-molecular-mass heparins(0828)with the modifications
and additional requirements below.
The mass-average relative molecular mass ranges between3800
and5000,with a characteristic value of about4500.
The degree of sulfatation is about2per disaccharide unit.
The potency is not less than90IU and not more than125IU of
anti-factor Xa activity per milligram,calculated with reference to
the dried substance.The anti-factor IIa activity is not less than
20.0IU and not more than35.0IU per milligram,calculated
with reference to the dried substance.The ratio of anti-factor
Xa activity to anti-factor IIa activity is between3.3and5.3.
PRODUCTION
保定学院分数线
Enoxaparin is produced by alkaline depolymerisation of benzyl
ester derivatives of heparin from porcine intestinal mucosa
under conditions that yield a product complying with the
structural requirements stated under Definition.
1920See the information ction on general monographs(cover pages)
EUROPEAN PHARMACOPOEIA 7.0
Enoxolone
IDENTIFICATION
Carry out identification test A as described in the monograph Low-molecular-mass heparins (0828)using enoxaparin sodium CRS .
Carry out identification test C as described in the monograph Low-molecular-mass heparins (0828).The following requirements apply.
The mass-average relative molecular mass ranges between 3800and 5000.The mass percentage of
chains lower than 2000ranges between 12.0per cent and 20.0per cent.The mass percentage of chains between 2000and 8000ranges between 68.0per cent and 82.0per cent.
TESTS
Appearance of solution .The solution is clear (2.2.1)and not more intenly coloured than intensity 6of the range of reference solutions of the most appropriate colour (2.2.2,Method II ).
Dissolve 1.0g in 10mL of water R .pH (2.2.3):6.2to 7.7.
Dissolve 1.0g in carbon dioxide-free water R and dilute to 10.0mL with the same solvent.
Specific absorbance (2.2.25):14.0to 20.0(dried substance),determined at 231nm.
Dissolve 50.0mg in 100mL of 0.01M hydrochloric acid .Benzyl alcohol .Liquid chromatography (2.2.29).Internal standard solution :1g/L solution of 3,4-dimethylphenol R in methanol R .
Test solution .Dissolve about 0.500g of the substance to be examined in 5.0mL of 1M sodium hydroxide .Allow to stand for 1h.Add 1.0mL of glacial acetic acid R and 1.0mL of the internal standard solution and dilute to 10.0mL with water R .Reference solution .Prepare a 0.25g/L solution of benzyl alcohol R in water R .Mix 0.50mL of this solution with 1.0mL of the internal standard solution and dilute to 10.0mL with water R .Precolumn :
—size :l =0.02m,Ø=4.6mm;
—stationary pha :octylsilyl silica gel for chromatography R (5μm).Column :
—size :l =0.15m,Ø=4.6mm;
—stationary pha :octylsilyl silica gel for chromatography R (5μm).
Mobile pha :methanol R ,acetonitrile R ,water R (5:15:80V/V/V ).
Flow rate :1mL/min.
Detection :spectrophotometer at 256nm.
From the chromatogram obtained with the reference solution,calculate the ratio (R 1)of the height of the peak due to benzyl alcohol to the height of the peak due to the internal standard.From the chromatogram obtained with the test solution,辐射4护甲代码
calculate the ratio (R 2)of the height of the peak due to benzyl alcohol to the height of the peak due to the internal standard.Calculate the percentage content (m/m )of benzyl alcohol using the following expression:
奇观的意思
m =mass of the substance to be examined,in grams.Limit :—benzyl alcohol :maximum 0.1per cent m/m .Sodium (2.2.23,Method I ):11.3per cent to 13.5per cent (dried
substance).
01/2008:1511corrected 6.0
ENOXOLONE
Enoxolonum
C 30H 46O 4M r 470.7
[471-53-4]
DEFINITION
(20β)-3β-Hydroxy-11-oxo-olean-12-en-29-oic acid.
Content :98.0per cent to 101.0per cent (dried substance).CHARACTERS
Appearance :white or almost white crystalline powder.
Solubility :practically insoluble in water,soluble in ethanol,sparingly soluble in methylene chloride.It shows polymorphism (5.9).
乡村文明
IDENTIFICATION First identification:A.
Second identification:B,C.
A.Examine by infrared absorption spectrophotometry (2.2.24).Comparison :enoxolone CRS .
If the spectra obtained in the solid state show differences,dissolve 0.2g of the substance to be examined and 0.2g of the reference substance parately in 6mL of ethanol R .Boil under a reflux condenr for 1h and add 6mL of water R .A precipitate is formed.Cool to about 10°C and filter with the aid of vacuum.Wash the precipitate with 10mL of alcohol R ,dry in an oven at 80°C and record new spectra.B.Thin-layer chromatography (2.2.27).
Test solution .Dissolve 10mg of the substance to be
examined in methylene chloride R and dilute to 10mL with the same solvent.
Reference solution.Dissolve 10mg of enoxolone CRS in methylene chloride R and dilute to 10mL with the same solvent.
Plate :TLC silica gel plate R .
Mobile pha :glacial acetic acid R ,acetone R ,methylene chloride R (5:10:90V/V/V ).Application :5μL.
Development :over 2/3of the plate.Drying :in air for 5min.
Detection :spray with anisaldehyde solution R and heat at 100-105°C for 10min.
Results :the principal spot in the chromatogram obtained
with the test solution is similar in position,colour and size
to the principal spot in the chromatogram obtained with the
reference solution.C.Dissolve 50mg in 10mL of methylene chloride R .To 2mL
of this solution,add 1mL of acetic anhydride R and 0.3mL of sulfuric acid R .A pink colour is produced.General Notices (1)apply to all monographs and other texts
1921
