EUROPEAN PHARMACOPOEIA 7.0Docetaxel
trihydrate TESTS Acidity or alkalinity .Dissolve 0.1g in water R with gentle heating and dilute to 10mL with the same solvent.Add 0.1mL of methyl red solution R and 0.2mL of 0.01M sodium hydroxide .The solution is yellow.Add 0.4mL of 0.01M hydrochloric acid .The solution is red.Optical rotation (2.2.7):−0.05°to +0.05°.Dissolve 0.50g in methanol R and dilute to 10.0mL with the same solvent.Absorbance (2.2.25):maximum 0.04at 480nm.Dissolve 0.5g in
a mixture of equal volumes of methanol R and
of water R with heating,if necessary,at 30-35°C and dilute to 25mL with the same mixture of solvents.Cool quickly.Examine immediately.Related substances .Liquid chromatography (2.2.29).Sol
vent mixture :mobile pha B,mobile pha A (35:65V/V ).Test solution .Dissolve 0.10g of the substance to be examined in the solvent mixture and dilute to 20.0mL with the solvent mixture.Reference solution (a).Dilute 4.0mL of the test solution to
100.0mL with a 0.05g/L solution of anisaldehyde R in the solvent mixture.Dilute 1.0mL of this solution to 10.0mL with the solvent mixture.Reference solution (b).Dilute 5.0mL of the test solution to 100.0mL with the solvent mixture.Dilute 1.0mL of this solution to 10.0mL with the solvent mixture.Reference solution (c).
Dissolve the contents of a vial of dobutamine impurity mixture CRS (impurities A,B and C)in 1.0mL of the solvent mixture.Column :新目标英语七年级上册
—size :l =0.15m,Ø=4.6mm;
—stationary pha :octadecylsilyl silica gel for chromatography R (5μm).
Mobile pha :—mobile pha
A
:dissolve
2.60g of sodium octanesulfonate R
in 1000mL of water R ,add 3mL of triethylamine R and
连衣裙 英语
adjust to pH 2.5with phosphoric acid R ;—mobile pha B :acetonitrile R ,methanol R (18:82V/V );
Time (min)Mobile pha A (per cent V/V )Mobile pha B (per cent V/V )
0-56535
5-2065→2035→80
20-252080
Flow rate :1mL/min.
Detection :spectrophotometer at 280nm.Injection :20μL.Identification of impurities :u the chromatogram supplied
with dobutamine
impurity
mixture CRS and the chromatogram obtained with reference solution (c)to identify the peaks due to impurities A,B and C.Relative retention with reference to dobutamine (retention time =about 12min):impurity A =about 0.3;impurity B =about 0.5;impurity C =about 1.4.System suitability :reference solution (a):
—resolution :minimum 4.0between the peaks due to
dobutamine and anisaldehyde.Limits :
—correction factor :for the calculation of content,multiply the
peak area of impurity B by 1.4;—impurities A,B,C :
for each impurity,not more 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 0.2times the area of the principal peak in the chromatogram obtained with reference solution (b)(0.10per cent);—total高考改革 英语
:not more than twice the area of the principal peak in the chromatogram obtained with the reference sculley
solution (b)(1per cent);
—disregard limit :0.1times the area of the principal peak in the chromatogram obtained with reference solution (b)(0.05per 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 .Loss
on drying (2.2.32):maximum 0.5per cent,determined on 1.000g by drying in an oven at 105°C.Sulfated
ash (2.4.14):maximum 0.1per cent,determined on 1.0g.ASSAY
In order to avoid overheating in the reaction medium,mix thoroughly
throughout and stop the titration immediately after the end-point has been reached.Dissolve
0.250g in 10mL of anhydrous formic acid R .Add 50mL of acetic anhydride R .Titrate with 0.1M perchloric acid ,determining the end-point potentiometrically (2.2.20).1
mL of 0.1M perchloric acid is equivalent to 33.79mg
of C 18H 24ClNO 3.
STORAGE
Protected from light.
IMPURITIES
Specified impurities:A,B,
C.
A.4-(2-aminoethyl)benzene-1,2-diol
(dopamine),
B.
4-(4-hydroxyphenyl)butan-2-one,C.(2RS )-N -[2-(3,4-dimethoxyphenyl)ethyl]-4-(4-
methoxyphenyl)butan-2-amine.
01/2010:2449
DOCETAXEL
TRIHYDRATE
Docetaxelum
trihydricum C 43H 53NO 14,3H 2O M r 862[148408-66-6]General Notices (1)apply to all monographs and other texts 1881
Docetaxel trihydrate EUROPEAN PHARMACOPOEIA
7.0
DEFINITION
1,7β,10β-Trihydroxy-9-oxo-5β,20-epoxytax-11-ene-
2α,4,13α-triyl4-acetate2-benzoate13-[(2R,3S)-3-
[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate],trihydrate.
Content:97.5per cent to102.0per cent(anhydrous substance). CHARACTERS
Appearance:white or almost white crystalline powder. Solubility:practically insoluble in water,freely soluble in anhydrous ethanol,soluble in methylene chloride. IDENTIFICATION
A.Specific optical rotation(e Tests).
B.Infrared absorption spectrophotometry(2.2.24).
Comparison:docetaxel trihydrate CRS.
TESTS
Appearance of solution.The solution is not more opalescent than reference suspension II(2.2.1)and not more intenly coloured than reference solution B5(2.2.2,Method I). Dissolve1.0g in anhydrous ethanol R and dilute to20mL with the same solvent.
Specific optical rotation(2.2.7):−38.5to−41.5(anhydrous substance).
Dissolve0.250g in methanol R and dilute to25.0mL with the same solvent.
Related substances.Liquid chromatography(2.2.29). Solvent mixture:acetic acid R,acetonitrile R1,water R (0.05:50:50V/V/V).
Test solution.Dissolve50.0mg of the substance to be examined in2.5mL of anhydrous ethanol R and dilute to50.0mL with the solvent mixture.
Reference solution(a).Dissolve50.0mg of docetaxel trihydrate CRS in2.5mL of anhydrous ethanol R and dilute to 50.0mL with the solvent mixture.
Reference solution(b).Dilute1.0mL of the test solution
to100.0mL with the solvent mixture.Dilute1.0mL of this solution to10.0mL with the solvent mixture.
Reference solution(c).Dissolve5mg of docetaxel for system suitability CRS(containing impurities A,B and C)in0.25mL of anhydrous ethanol R and dilute to5.0mL with the solvent mixture.
Column:
—size:l=0.15m,Ø=4.6mm;
—stationary pha:end-capped octadecylsilyl silica gel for chromatography R(3.5μm);
—temperature:45°C.
puppet中文Mobile pha:
—mobile pha A:water R;
—mobile pha B:acetonitrile R1;
Time (min)Mobile pha A
(per cent V/V)
Mobile pha B
(per cent V/V)
0-97228
9→3972→2828→72
Flow rate:1.2mL/min.
Detection:spectrophotometer at232nm.
Injection:10μL of the test solution and reference solutions(b) and(c).Identification of impurities:u the chromatogram supplied with docetaxel for system suitability CRS and the chromatogram obtained with reference solution(c)to identify the peaks due to impurities A,B and C.
Relative retention with reference to docetaxel(retention
time=about27min):impurity A=about0.97;impurity B=about 1.08;impurity C=about1.13.
System suitability:reference solution(c):
—resolution:minimum4.0between the peaks due to impurity A and docetaxel.
Limits:
nirvana—correction factor:for the calculation of content,multiply the peak area of impurity A by1.6;
—impurity A:not more than5times the area of the principal peak in the chromatogram obtained with reference
solution(b)(0.5per cent);
—impurities B,C:for each impurity,not more than3times the area of the principal peak in the chromatogram obtained with reference solution(b)(0.3per cent);
—unspecified impurities:for each impurity,not more than the area of the principal peak in the chromatogram obtained
英语四级考试题with reference solution(b)(0.10per cent);
—total:not more than10times the area of the principal peak in the chromatogram obtained with reference solution(b)
(1.0per cent);
simple是什么意思—disregard limit:0.5times the area of the principal peak in the chromatogram obtained with reference solution(b)
(0.05per cent).
Heavy metals(2.4.8):maximum20ppm.
Dissolve,using sonication,1.0g in a mixture of15volumes of water R and85volumes of dimethylformamide R and dilute to 20mL with the same mixture of solvents.12mL of the solution complies with test B.Prepare the reference solution using lead standard solution(1ppm Pb)obtained by diluting lead standard solution(100ppm Pb)R with a mixture of15volumes of water R and85volumes of dimethylformamide R.
Water(2.5.32):5.0per cent to7.0per cent.
Inject200μL of a100mg/mL solution of the substance to be examined in dimethylformamide R.
Sulfated ash(2.4.14):maximum0.1per cent,determined on 1.0g.
Bacterial endotoxins(2.6.14):less than0.3IU/mg,if intended for u in the manufacture of parenteral preparations without a further appropriate procedure for the removal of bacterial endotoxins.
ASSAY
Liquid chromatography(2.2.29)as described in the test for related substances with the following modifications. Injection:10μL of the test solution and reference solution(a).
Calculate the percentage content of C
43
H
53
NO
14
from the declared content of docetaxel trihydrate CRS.
STORAGE
Protected from light.
IMPURITIES
dowSpecified impurities:A,B,C.
Other detectable impurities(the following substances would, if prent 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 u (2034).It is therefore not necessary to identify the impurities for demonstration of compliance.See also5.10.Control of impurities in substances for pharmaceutical u):D.
1882See the information ction on general monographs(cover pages)
EUROPEAN PHARMACOPOEIA 7.0Docusate
sodium
A.1,7β,10β-trihydroxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 13-[(2R ,3S )-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate]2-[(2E )-2-methylbut-2-enoate](2-O -desbenzoyl-2-O
-tiglyldocetaxel),B.1,7β-dihydroxy-9,10-dioxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benz
oate 13-[(2R ,3S )-3-
[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate]
(10-dehydroxy-10-oxodocetaxel),C.1,7α,10β-trihydroxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-[(2R ,3S )-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate](7-epi
-docetaxel),D.1,7α-dihydroxy-9,10-dioxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-[(2R ,3S )-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate](10-dehydroxy-10-oxo-7-epi -docetaxel).01/2008:1418DOCUSATE SODIUM Natrii
docusas C 20H 37NaO 7S M r 444.6[577-11-7]DEFINITION
Sodium 1,4-bis[(2-ethylhexyl)oxy]-1,4-dioxobutane-2-sulfonate.
Content :98.0to 101.0per cent (anhydrous substance).
CHARACTERS
Appearance :white or almost white,waxy mass or flakes,
hygroscopic.Solubility :sparingly soluble in water,freely soluble in ethanol
(96per cent)and in methylene chloride.IDENTIFICATION
A.Infrared absorption spectrophotometry (2.2.24).
Preparation :place about 3mg of the substance to be examined on a sodium chloride plate,add 0.05
mL of acetone R and immediately cover with another sodium
chloride plate.
Rub the plates together to dissolve the
substance to be examined,slide the plates apart and allow
the acetone to evaporate.Comparison :ference spectrum of docusate
sodium .B.In a crucible,ignite 0.75g in the prence of dilute sulfuric acid R ,until an almost white
residue
is obtained.
Allow to
cool and take up the residue with 5mL of water R .Filter.2mL of the filtrate gives reaction (a)of sodium (2.3.1).
TESTS
Alkalinity .Dissolve 1.0g in 100mL of a mixture of equal volumes of methanol R and water R ,previously neutralid to methyl red solution R .Add 0.1mL of methyl red solution R .Not more than 0.2mL of 0.1M hydrochloric acid is required to change the colour of the indicator to red.
Related non-ionic substances .Gas chromatography (2.2.28).
Internal standard solution .Dissolve 10mg of methyl behenate R in hexane R and dilute to 50mL with the same
solvent.Test solution (a).Dissolve 0.10g of the substance to be
examined in 2.0mL of the internal standard solution and dilute
to 5.0mL with hexane R .Pass the solution,at a rate of about 1.5mL/min,through a column 10mm in internal diameter,packed
with
5
g of basic aluminium oxide R and previously
washed with 25mL of hexane R .Elute with 5mL of hexane Rdeborah rowe
and discard the eluate.Elute with 20mL of a mixture of equal volumes of ether R and hexane R .Evaporate the eluate to
dryness and dissolve the residue in 2.0mL of hexane R .Test solution (b).Prepare as described for test
solution
(a)but
dissolving 0.10g of the substance to be examined in hexane R ,
diluting to 5.0mL with the same solvent,and using a new column.Reference solution .Dilute 2.0mL of the internal standard
solution to 5.0mL with hexane R .Column :
—material :glass,—size :l =2m,Ø=2mm,
—
stationary pha :silanid diatomaceous earth for gas chromatography R impregnated with 3per cent m/m
of
polymethylphenylsiloxane R .Carrier gas :nitrogen for chromatography R .
Flow rate :30mL/min.
Temperature :
—column :230°C,
—injection port and detector :280°C.
Detection :flame ionisation.
Injection :1μL.
Run time :2.5times the retention time of the internal standard.
System suitability :there is no peak with the same retention time as the internal standard in the chromatogram obtained with test solution (b).
General Notices (1)apply to all monographs and other texts 1883
