EUROPEAN PHARMACOPOEIA 7.0Prednisolone
acetate TESTS
Specific optical rotation (2.2.7):+96to +102(dried substance).
Dissolve 0.250g in dioxan R and dilute to 25.0mL with the
same solvent.Related substances .Liquid chromatography (2.2.29).
Test solution.Dissolve 25.0mg of the substance to be examined in 2mL of tetrahydrofuran R and dilute to 10.0mL with water R .Reference solution (a).Dissolve 2mg of prednisolone CRS and
2mg of hydrocortisone CRS (impurity A)in the mobile pha and dilute to 100.0mL with the mobile pha.Reference solution (b).Dilute 1.0mL of the test solution to 100.0mL with the mobile pha.Column :
—size :l =0.25m,Ø=4.6mm;
—stationary pha :ba-deactivated end-capped octadecylsilyl silica gel for chromatography R (5μm);
—temperature :45°C.
Mobile pha :in a 1000mL volumetric flask,mix 220mL of tetrahydrofuran R with 700mL of water R and allow to equilibrate;dilute to 1000mL with water R and mix again.
Flow rate :1mL/min.Detection :spectrophotometer at 254nm.Equilibration :with the mobile pha for about 30min.Injection :20μL;inject the solvent mixture of the test solution as a blank.Run time :4.5times the retention time of prednisolone.Retention time :prednisolone =about 14min;impurity A =about 15.5min.System suitability :reference solution (a):—resolution :minimum 2.2between the peaks due to
prednisolone and impurity A;if necessary,adjust the concentration of tetrahydrofuran R in the mobile pha.Limits :—any impurity :for each impurity,not more than the area
of the principal peak in the chromatogram obtained with reference solution (b)(1per cent)and not more than one such peak has an area greater than 0.5times the area of the
principal peak in the chromatogram obtained with reference solution (b)(0.5per cent);—total :not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b)(2per cent);—disregard limit :0.05times the area of the principal peak in the chromatogram obtained with reference solution (b)(0.05per cent).Loss on drying (2.2.32):maximum 1.0per cent,determined on 0.500g by drying in an oven at 105°C.ASSAY Dissolve 0.100g
in
ethanol (96per
cent)
R
菠萝派>激运票有什么用and dilute to 100.0mL with the same solvent.Dilute 2.0mL of this solution to 100.0mL with ethanol (96per cent)R .Measure the absorbance (2.2.25)at the absorption maximum at 243.5nm.Calculate the content of C 21H 28O 5taking
the specific absorbance to be 415.STORAGE In an airtight container,protected from light.IMPURITIES Specified impurities :A
. A.11β,17,21-trihydroxypregn-4-ene-3,20-dione (hydrocortisone).01/2008:0734corrected 6.0PREDNISOLONE ACETATE Prednisoloni
锤子坚果3
acetas
C 23H 30O 6M r 402.5[52-21-1]DEFINITION
11β,17-Dihydroxy-3,20-dioxopregna-1,4-dien-21-yl acetate.Content :97.0per cent to 103.0per cent (dried substance).CHARACTERS
Appearance :white or almost white,crystalline powder.Solubility
:practically insoluble in water,slightly soluble in ethanol (96per cent)and in methylene chloride.IDENTIFICATION
First identification:A,B.
Second identification:B,C,D.
A.Infrared absorption spectrophotometry (2.2.24).
Comparison :prednisolone acetate CRS .
B.Thin-layer chromatography (2.2.27).
Test
solution.
Dissolve
10mg of the substance to be
examined in
a mixture of 1volume of methanol R and 9
volumes of methylene chloride R and dilute to 10mL with
the same mixture of solvents.Reference
solution (a).Dissolve 20mg of prednisolone acetate
CRS in a mixture of 1volume of methanol R and 9volumes of methylene chloride R and dilute to 20mL with the same mixture of solvents.Reference
solution (b).Dissolve 10
mg of prednisolone pivalate CRS in reference solution (a)and dilute to 10mL with the same solution.Plate :TLC silica gel plate F 254R .
Mobile
pha :add a mixture of 1.2volumes of water R and
8volumes of methanol R to a mixture of 15volumes of ether R and 77volumes of methylene chloride R .
Application :5μL.
Development :over a path of 15cm.
Drying :in air.
Detection A :examine in ultraviolet light at 254nm.
Results
A :the principal spot in the chromatogram obtained with the test solution is similar in position and size to the
principal spot in the chromatogram obtained with reference solution (a).Detection
B :spray with alcoholic solution of sulfuric acid R .
Heat at 105°C for 10min or until the spots appear.Allow to cool.Examine in daylight and in ultraviolet light at 365nm.
System suitability :reference solution (b):
—the chromatogram obtained shows 2clearly parated spots.General Notices (1)apply to all monographs and other texts 2787
Prednisolone acetate EUROPEAN PHARMACOPOEIA
7.0
Results B:the principal spot in the chromatogram obtained with the test solution is similar in position,colour in daylight, fluorescence in ultraviolet light at365nm and size to the principal spot in the chromatogram obtained with reference solution(a).
C.Add about2mg to2mL of sulfuric acid R and shake to
dissolve.Within5min,an inten red colour develops.When examined in ultraviolet light at365nm,a reddish-brown
fluorescence is en.Add the solution to10mL of water R and mix.The colour fades and there is greenish-yellow
fluorescence in ultraviolet light at365nm.
D.About10mg gives the reaction of acetyl(2.3.1).
TESTS
Specific optical rotation(2.2.7):+128to+137(dried substance).
Dissolve70.0mg in methanol R2and dilute to20.0mL with the same solvent.
Related substances.Liquid chromatography(2.2.29).Prepare the solutions immediately before u.
Buffer solution pH4.Mix1volume of dilute hydrochloric acid R,5volumes of a68.1g/L solution of sodium acetate R, 15volumes of a37.3g/L solution of potassium chloride R and 79volumes of water R.
Solvent mixture.Mix equal volumes of acetonitrile R and buffer solution pH4.
Test solution.Dissolve25.0mg of the substance to be examined in methanol R and dilute to10.0mL with the same solvent. Reference solution(a).Dissolve2mg of prednisolone acetate CRS and2mg of hydrocortisone acetate CRS (impurity A)in the solvent mixture and dilute to100.0mL with the solvent mixture.
Reference solution(b).Dilute1.0mL of the test solution
to100.0mL with the solvent mixture.Dilute2.0mL of this solution to10.0mL with the solvent mixture.
Reference solution(c).Dissolve5mg of prednisolone acetate for peak identification CRS(containing impurities A,B and C)in the solvent mixture and dilute to50mL with the solvent mixture.
Column:
—size:l=0.25m,Ø=4.6mm;
—stationary pha:end-capped octadecylsilyl silica gel for chromatography R(5μm);
—temperature:40°C.
Mobile pha:acetonitrile R,water R(350:650V/V).
Flow rate:1mL/min.
Detection:spectrophotometer at254nm.
Injection:20μL.
Run time:2.5times the retention time of prednisolone acetate. Identification of impurities:u the chromatogram supplied with prednisolone acetate for peak identification 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 prednisolone acetate (retention time=about17min):impurity B=about0.4; impurity A=about1.1;impurity C=about2.0.
System suitability:reference solution(a):
—resolution:minimum2.0between the peaks due to prednisolone acetate and impurity A.
Limits:
—impurities A,B:for each impurity,not more than5times the area of the principal peak in the chromatogram obtained with reference solution(b)(1.0per cent);
—impurity C:not more than2.5times 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
0.5times the area of the principal peak in the chromatogram
obtained 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)
(2.0per cent);
—disregard limit:0.25times the area of the principal peak in the chromatogram obtained with reference solution(b)
(0.05per cent).红黑游戏
Loss on drying(2.2.32):maximum0.5per cent,determined on 1.000g by drying in an oven at105°C.
ASSAY
Dissolve0.100g in ethanol(96per cent)R and dilute to 100.0mL with the same solvent.Dilute2.0mL of this solution to100.0mL with ethanol(96per cent)R.Measure the absorbance(2.2.25)at the absorption maximum at243nm. Calculate the content of C
23
H
30
O
主体结构包括哪些
6
重组过程taking the specific absorbance to be370.
STORAGE
Protected from light.
IMPURITIES
Specified 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,
E.
A.11β,17-dihydroxy-3,20-dioxopregn-4-en-21-yl acetate
(hydrocortisone
教育目的是什么
马嵬驿民俗文化村
acetate),
B.11β,17,21-trihydroxypregna-1,4-diene-3,20-dione
(prednisolone),
C.R1=R2=O-CO-CH
3
:17-hydroxy-3,20-dioxopregna-1,4-diene-11β,21-diyl diacetate(prednisolone11,21-diacetate),
D.R1=OH,R2=H:11β,17-dihydroxypregna-1,4-diene-
3,20-dione,
E.17-hydroxy-3,20-dioxopregna-1,4,9(11)-trien-21-yl acetate.
2788See the information ction on general monographs(cover pages)
EUROPEAN PHARMACOPOEIA 7.0Prednisolone
pivalate
01/2008:0736corrected 6.0PREDNISOLONE PIVALATE Prednisoloni
pivalas C 26H 36O 6M r 444.6[1107-99-9]DEFINITION 11β,17-Dihydroxy-3,20-dioxopregna-1,4-dien-21-yl 2,2-dimethylpropanoate.Content :97.0per cent to 103.0per cent (dried substance).CHARACTERS Appearance :white or almost white,crystalline powder.Solubility :practically insoluble in water,slightly soluble in ethanol (96per cent),soluble in methylene chloride.mp:about 229°C,with decomposition.IDENTIFICATION First identification:B,C .Second identification:A,C,D .A.Dissolve 10.0mg in anhydrous ethanol R and
dilute
to
100.0mL with the same solvent.Place 2.0mL of this solution in a ground-glass-stoppered tube,add 10.0mL of phenylhydrazine-sulfuric acid solution R ,mix and heat in a water-bath at 60°C for 20min.Cool immediately.The absorbance (2.2.25)at the absorption maximum at 415nm is 0.20to 0.30.B.Infrared absorption spectrophotometry (2.2.24).Comparison :prednisolone pivalate CRS .If the spectra obtained in the solid state show differences,dissolve the substance to be examined and the reference substance parately in the minimum volume of ethanol (96per cent)R ,evaporate to dryness on a water-bath and record new spectra using the residues.C.Thin-layer chromatography (2.2.27).Solvent mixture :methanol R ,methylene chloride R (1:9V/V ).Test solution
.Dissolve 10mg of the substance to be examined in the solvent mixture and dilute to 10mL with the solvent mixture.Reference solution
(a)
.Dissolve 10mg of prednisolone pivalate CRS in the solvent mixture and dilute to 10mL with the solvent mixture.Reference solution (b).Dissolve 10mg of prednisolone acetate CRS in the solvent mixture and dilute to 10mL with the solvent mixture.Dilute 5mL of this solution to 10mL with reference solution (a).Plate :TLC silica gel F 254plate R .Mobile pha :add a mixture of 1.2volumes of water R and 8volumes of methanol R to a mixture of 15volumes of ether R and 77volumes of methylene chloride R .Application :5μL.Development :over a path of 15cm.Drying :in air.Detection A :examine in ultraviolet light at 254nm.Results A :the principal spot in the chromatogram obtained with the test solution is similar in position and size to the principal spot in the chromatogram obtained with
reference
solution (a).Detection
B :spray with alcoholic solution of sulfuric
acid R ,heat at 120°C for 10min or until the spots appear,and allow to cool;examine in daylight and in ultraviolet light
at 365nm.Results B :the principal spot in the chromatogram obtained
with the test solution is similar in position,colour in daylight,fluorescence in ultraviolet light at 365nm and size to the principal spot in the chromatogram obtained with reference
solution (a).System suitability :reference solution (b):
—the chromatogram shows 2clearly parated spots.
D.To 2mL of sulfuric acid R ,add about 2mg and shake to
dissolve.Within 5min,an inten red colour develops.When examined
in ultraviolet light at 365nm,a reddish-brown fluorescence is en.Add this solution to 10mL of water R and mix.The colour fades and there is greenish-yellow fluorescence in ultraviolet light at 365nm.
TESTS
Specific optical rotation (2.2.7):+104to +112(dried substance).
Dissolve 0.250g in dioxan R and dilute to 25.0mL with the same solvent.Related substances .Liquid
chromatography (2.2.29).Test
solution .Dissolve 62.5mg of the substance to be examined in 2mL of a mixture of 1volume of water R and 4volumes of tetrahydrofuran R and dilute to 25.0mL with the mobile pha.
Reference solution (a).Dissolve 25mg of prednisolone acetate CRS ,25mg of cortisone acetate CRS and 25mg of
prednisolone pivalate CRS in 2mL of a mixture of 1volume of water R and 4volumes of tetrahydrofuran R and dilute to 25.0mL with the mobile pha.Dilute 1.0mL of this solution to 25.0mL with the mobile pha.Reference solution (b).Dilute 1.0mL of the test solution to
50.0mL with the mobile pha.Column :
—size :l =0.15m,Ø=4.6mm;
—stationary pha :octadecylsilyl silica gel for
chromatography R (5μm).
Mobile pha :carefully mix 19mL of butyl acetate R1with
37mL of tetrahydrofuran R and 213mL of ethylene glycol monomethyl
ether R ,then add with 231mL of water R ;mix,allow to equilibrate for 1h and filter through a 0.45μm filter.Flow rate :1mL/min.
Detection :spectrophotometer at 254nm.
Equilibration :with the mobile pha for about 30
min.
Injection :20μL.
Run time :1.5times the retention time of prednisolone pivalate.
Retention time :prednisolone acetate =about 3.5min;cortisone acetate =about 4.5min;prednisolone pivalate =about 13min.
System suitability :reference solution (a):—resolution :minimum 2.5between the
peaks due to prednisolone acetate and cortisone acetate;if necessary,adjust the concentration of wat
er in the mobile pha.Limits :
—any impurity :for each impurity,not more than the area of the principal peak in the chromatogram obtained with reference solution (b)(2.0per cent),and not more than one such peak has an area greater than 0.5times the area of the
principal peak in the chromatogram obtained with reference solution (b)(1.0per cent);
—total
:not
more than 1.25times the area of the principal peak
in the chromatogram obtained with reference solution (b)
(2.5per cent);General Notices (1)apply to all monographs and other texts 2789
