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PA/PH/Exp. 10A/T (07) 103 ANP
BILINGUE
GROUP 10A
Phenobarbital
Phnobarbital
Phenobarbitalum
Monograph N: 201
Cette monographie est soumise aux Autorits nationales pour commentaires et elle sera publie simultanment
dans le prochain numro de Pharmeuropa (Pharmeuropa 20.2).
Programme spcial de rvision.
This monograph is submitted to National Authorities for comment and will be simultaneously published in the
next issue of Pharmeuropa (Pharmeuropa 20.2).
Special revision programme.
Distribution
For action:
ANP National Pharmacopoeia Authorities
For information :
10A Organic chemistry Synthetic Products
PRES Praesidium
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XXXX:0201
PHENOBARBITAL
Phenobarbitalum
C12H12N2O3
[50-06-6]
Mr 232.2
DEFINITION
5-Ethyl-5-phenylpyrimidine-2,4,6(1H,3H,5H)-trione.
Content : 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder or colourless crystals.
Solubility : very slightly soluble in water, freely soluble in ethanol (96 per cent).
It forms water-soluble compounds with alkali hydroxides, carbonates and ammonia.
IDENTIFICATION
First identification : A, B.
Second identification : A, C, D.
A. Determine the melting point (2.2.14) of the substance to be examined. Mix equal parts
of the substance to be examined and phenobarbital CRS ; determine the melting point
of the mixture. The difference between the 2 melting points (which are about 176 C)
is not greater than 2 C.
B. Infrared absorption spectrophotometry (2.2.24).
Comparison : phenobarbital CRS.
C. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 0.1 g of the substance to be examined in ethanol (96 per cent) R
and dilute to 100.0 ml with the same solvent.
Reference solution. Dissolve 0.1 g of phenobarbital CRS in ethanol (96 per cent) R
and dilute to 100.0 ml with the same solvent.
Plate : TLC silica gel GF254 plate R.
E1
E3
1. impurity A
2. impurity B
3. impurity C
4. phenobarbital
Figure 0201.-1. Chromatogram for the test for related substances : solution of
phenobarbital spiked with impurities A, B and C
Loss on drying (2.2.32) : maximum 0.5 per cent, determined on 1.000 g by drying in
an oven at 105 C.
Sulphated ash (2.4.14) : maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.100 g in 5 ml of pyridine R. Add 0.5 ml of thymolphthalein solution R and
10 ml of silver nitrate solution in pyridine R. Titrate with 0.1 M ethanolic sodium
hydroxide until a pure blue colour is obtained. Carry out a blank titration.
1 ml of 0.1 M ethanolic sodium hydroxide is equivalent to 11.61 mg of C12H12N2O3.
IMPURITIES
Specified impurities : A, B.
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) : C.
E4
A. R = NH : 2,6-diamino-5-ethyl-5-phenylpyrimidin-4(5H)-one,
B. R = O : 6-amino-5-ethyl-5-phenylpyrimidine-2,4(3H,5H)-dione,
C. 5-methyl-5-phenylpyrimidine-2,4,6(1H,3H,5H)-trione.
E5
PHNOBARBITAL
Phenobarbitalum
C12H12N2O3
[50-06-6]
Mr 232,2
DFINITION
5-Ethyl-5-phnylpyrimidine-2,4,6(1H,3H,5H)-trione.
Teneur : 99,0 pour cent 101,0 pour cent (substance dessche).
CARACTRES
Aspect : poudre cristalline, blanche ou sensiblement blanche, ou cristaux incolores.
Solubilit : trs peu soluble dans leau, facilement soluble dans lthanol 96 pour cent.
Le phnobarbital donne des composs solubles dans leau avec les hydroxydes alcalins,
les carbonates alcalins et lammoniaque.
IDENTIFICATION
Premire identification : A, B.
Seconde identification : A, C, D.
A. Dterminez le point de fusion (2.2.14) du phnobarbital. Mlangez en proportions
gales de la substance examiner et du phnobarbital SCR, puis dterminez le point
de fusion du mlange. La diffrence entre les 2 points de fusion observs vers 176 C
nest pas suprieure 2 C.
B. Spectrophotomtrie dabsorption dans linfrarouge (2.2.24).
Comparaison : phnobarbital SCR.
C. Chromatographie sur couche mince (2.2.27).
Solution examiner. Dissolvez 0,1 g de phnobarbital dans de lthanol 96 pour
cent R et compltez 100,0 ml avec le mme solvant.
Solution tmoin. Dissolvez 0,1 g de phnobarbital SCR dans de lthanol 96 pour
cent R et compltez 100,0 ml avec le mme solvant.
Plaque : plaque au gel de silice GF254 pour CCM R.
F1
1. impuret A
2. impuret B
3. impuret C
4. phnobarbital
F3
A. R = NH : 2,6-diamino-5-thyl-5-phnylpyrimidin-4(5H)-one,
B. R = O : 6-amino-5-thyl-5-phnylpyrimidine-2,4(3H,5H)-dione,
C. 5-mthyl-5-phnylpyrimidine-2,4,6(1H,3H,5H)-trione.
F5