Nicorandil EUROPEAN PHARMACOPOEIA
8.6
System suitability :test solution (b):
–resolution :minimum 1.0between the 2peaks due to the diastereoisomers of naftidrofuryl.Limits :test solution (a):
–impurity F :for the sum of the areas of the 2peaks,maximum 0.20per cent of the sum of the areas of the 2peaks due to naftidrofuryl (0.20per cent);–impurity E :maximum 0.20per cent of the sum of the areas of the 2peaks due to naftidrofuryl (0.20per cent);–impurity D :maximum 0.10per cent of the sum of the areas of the 2peaks due to naftidrofuryl (0.10per cent);–any other impurity :for each impurity,maximum
0.10per cent of the sum of the areas of the 2peaks due to naftidrofuryl (0.10per cent);–total :maximum 0.50per cent of the sum of the areas of the 2peaks due to naftidroduryl (0.50per cent);–disregard limit :0.02per cent of the sum of the areas of the 2peaks due to naftidrofuryl (0.02per cent);disregard any peaks due to impurity B.
Diastereoisomer ratio .Gas chromatography (2.2.28)as described in test B for related substances.Limits :test solution (b):
–first eluting naftidrofuryl diastereoisomer :minimum 30per cent of the sum of the areas of the 2peaks due to naftidrofuryl.
Heavy metals (2.4.8):maximum 10ppm.
In a silica crucible,mix thoroughly 1.0g of the substance to be examined with 0.5g of magnesium oxide R1.Ignite to dull redness until a homogeneous white or greyish-white mass is obtained.If after 30min of ignition the mixture remains coloured,allow to cool,mix using a fine glass rod and repeat the ignition.If necessary repeat the operation.Heat at 800±50°C for about 1h.Take up the residue with 2quantities,each of 5mL,of a mixture of equal volumes of hydrochloric acid R1and water R .Add 0.1
mL of phenolphthalein solution R and then concentrated ammonia R until a pink colour is obtained.Cool,add glacial acetic acid R until the solution is decolorised and add 0.5mL in excess.Filter if necessary and
wash the filter.Dilute to 20mL with water R .The solution
complies with test E.Prepare the reference solution using
10mL of lead standard solution (1ppm 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
Dissolve 0.350g in 50mL of anhydrous 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 47.36mg of C 26H 35NO 7.IMPURITIES
Specified impurities:A,B,C,D,E,
F.
A.2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2-yl)propanoic
acid, B.ethyl 2-[(naphthalen-1-yl)methyl]-3-(tetrahydrofuran-2-
yl)propanoate,
C.2-(diethylamino)ethyl 3-(naphthalen-1-yl)-2-[(naphthalen-
1-yl)methyl]propanoate,D.2-(diethylamino)ethyl 3-[(2RS )-tetrahydrofuran-2-
yl]propanoate,E.2-(diethylamino)ethyl (2RS )-2-[(furan-2-yl)methyl]-3-
(naphthalen-1-yl)propanoate,F.2-(diethylamino)ethyl 2-[(naphthalen-2-yl)methyl]-3-(tetrahydrofuran-2-yl)propanoate.01/2016:2332NICORANDIL
Nicorandilum
C 8H 9N 3O 4M r 211.2
[65141-46-0]
DEFINITION
2-[(Pyridin-3-ylcarbonyl)amino]ethyl nitrate.
Content :99.0per cent to 101.0per cent (anhydrous substance).CHARACTERS
Appearance :white or almost white,crystalline powder.Solubility :sparingly soluble in water,freely soluble in anhydrous ethanol,practically insoluble in heptane.
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).Comparison :nicorandil CRS .
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See the information section on general monographs (cover pages)
EUROPEAN PHARMACOPOEIA 8.6
Nicotinamide
TESTS
pH (2.2.3):5.5to 7.0.
Dissolve 0.25g in carbon dioxide-free water R and dilute to 25mL with the same solvent.
Related substances .Liquid chromatography (2.2.29).Prepare the solutions immediately before use.
Test solution .Dissolve 50mg of the substance to be examined in the mobile phase and dilute to 25.0mL with the mobile phase.
Reference solution (a).Dissolve 2mg of nicorandil
中草药大典impurity A CRS in the mobile phase using sonication and dilute to 25.0mL with the mobile phase.Dilute 1.0mL of the solution to 20.0mL with the test solution.
Reference solution (b).Dilute 1.0mL of the test solution to 100.0mL with the mobile phase.Dilute 1.0mL of this solution to 10.0mL with the mobile phase.Column :
–size :l =0.25m,Ø=4.6mm;
–stationary phase :end-capped octadecylsilyl silica gel for chromatography compatible with 100per cent aqueous mobile phases R (5μm).
bd留置针
Mobile phase :trifluoroacetic acid R ,triethylamine R ,tetrahydrofuran R ,water R (3:5:10:982V/V/V/V ).Flow rate :1.0mL/min.
Detection :spectrophotometer at 254nm.Injection :10μL.
宇称不
守恒Run time :1.5times the retention time of nicorandil.Identification of impurities :use the chromatogram obtained with reference solution (a)to identify the p
eak due to impurity A.
Relative retention with reference to nicorandil (retention time =about 19min):impurity A =about 0.9.System suitability :reference solution (a):
–resolution :minimum 2.5between the peaks due to impurity A and nicorandil.Calculation of percentage contents :
–for each impurity,use the concentration of nicorandil in reference solution (b).Limits :
–unspecified impurities :for each impurity,maximum 0.10per cent;
trx
–total :maximum 0.2per cent;–reporting threshold :0.05per cent.Sulfates (2.4.13):maximum 100ppm.
Dissolve 5.000g in 30mL of ethanol (50per cent V/V)R ,add 1mL of dilute hydrochloric acid R and dilute to 50.0mL with distilled water R .
Water (2.5.32):maximum 0.5per cent.
Dissolve 0.300g in a suitable solvent and dilute to 1.0mL with the same solvent.Inject 0.400mL of the solution through the septum.
Sulfated ash (2.4.14):maximum 0.1per cent,determined on 1.0g.
ASSAY
Dissolve 0.150g in 50mL of anhydrous 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 21.12mg of C 8H 9N 3O 4.
STORAGE
At a temperature of 2°C to 8°C.
IMPURITIES
广东工业大学学报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, 车载雷达天线
D.
A.2-[(pyridin-4-ylcarbonyl)amino]ethyl
nitrate,
B.N
-(2-hydroxyethyl)pyridine-3-carboxamide,
C.2-aminoethyl
pyridine-3-carboxylate,
D.3-(4,5-dihydro-1,3-oxazol-2-yl)pyridine.
01/2016:0047
NICOTINAMIDE
Nicotinamidum
C 6H 6N 2O M r 122.1
[98-92-0]
DEFINITION
Pyridine-3-carboxamide.
Content :99.0per cent to 101.0per cent (dried substance).CHARACTERS
Appearance :white or almost white,crystalline powder or colourless crystals.
Solubility :freely soluble in water and in anhydrous ethanol,slightly soluble in methylene chloride.
IDENTIFICATION First identification:B.
Second identification:A,C.
A.Melting point (2.2.14):128°C to 131°C.
B.Infrared absorption spectrophotometry (2.2.24).Comparison :nicotinamide CRS .
C.Thin-layer chromatography (2.2.27).
Test solution .Dissolve 5mg of the substance to be
examined in a mixture of equal volumes of ethanol (96per cent)R and water R and dilute to 5.0mL with the same mixture of solvents.
General Notices (1)apply to all monographs and other texts
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