Diosmin EUROPEAN PHARMACOPOEIA 8.

the contents of the flask immediately after the end of the

combustion to dissolve completely the combustion products.
Continue stirring for 1 h.
Reference solution. Dilute 2.0 mL of a 16.6 g/L solution of
potassium iodide R to 100.0 mL with water R. Dilute 10.0 mL
E. (Z)-7-[2-[(E)-(3S)-3-hydroxyoct-1-enyl]-5-oxocyclopent- of the solution to 100.0 mL with water R.
1-enyl]hept-5-enoic acid (PGB2), Introduce into a beaker 30 mL of a 200 g/L solution of
potassium nitrate R in 0.1 M nitric acid. Immerse the
electrodes and stir for 10 min. The potential of the solution
(nT1) must remain stable. Add 1 mL of the test solution and
measure the potential (nT2).
Introduce into a beaker 30 mL of a 200 g/L solution of
potassium nitrate R in 0.1 M nitric acid. Immerse the
F. (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E)-3-oxo-oct-1-enyl]- electrodes and stir for 10 min. The potential of the solution
5-oxocyclopentyl]hept-5-enoic acid (15-oxo-PGE2 ; must remain stable (nR1). Add 80 μL of the reference solution
15-keto-PGE2). and measure the potential (nR2).
The absolute value |nT2 - nT1| is not higher than the absolute
01/2008:1611 value |nR2 - nR1|.
Related substances. Liquid chromatography (2.2.29).
DIOSMIN Test solution. Dissolve 25.0 mg of the substance to be
examined in dimethyl sulfoxide R and dilute to 25.0 mL with
the same solvent.
Diosminum
Reference solution (a). Dissolve 25.0 mg of diosmin CRS in
dimethyl sulfoxide R and dilute to 25.0 mL with the same
solvent.
Reference solution (b). Dilute 5.0 mL of reference solution (a)
to 100.0 mL with dimethyl sulfoxide R.
Reference solution (c). Dissolve 5.0 mg of diosmin for system
suitability CRS in dimethyl sulfoxide R and dilute to 5.0 mL
with the same solvent.
C28H32O15 Mr 609 Column :
[520-27-4] – size : l = 0.10 m, Ø = 4.6 mm,
DEFINITION – stationary phase : octadecylsilyl silica gel for
chromatography R (3 μm),
7-[[6-O-(6-Deoxy-α-L-mannopyranosyl)-β-D-
glucopyranosyl]oxy]-5-hydroxy-2-(3-hydroxy-4- – temperature : 40 °C.
methoxyphenyl)-4H-1-benzopyran-4-one. Mobile phase : acetonitrile R, glacial acetic acid R, methanol R,
Substance obtained through iodine-assisted oxidation water R (2:6:28:66 V/V/V/V).
of (2S)-7-[[6-O-(6-deoxy-α-L-mannopyranosyl)-β- Flow rate : 1.5 mL/min.
D-glucopyranosyl]oxy]-5-hydroxy-2-(3-hydroxy-4- Detection : spectrophotometer at 275 nm.
methoxyphenyl)-2,3-dihydro-4H-1-benzopyran-4-one Injection : 10 μL loop injector ; inject the test solution and
(hesperidin) of natural origin. reference solutions (b) and (c).
Content : 90.0 per cent to 102.0 per cent (anhydrous substance). Run time : 6 times the retention time of diosmin.
CHARACTERS Relative retention with reference to diosmin (retention
Appearance : greyish-yellow or light yellow hygroscopic time = about 4.6 min) : impurity A = about 0.5,
powder. impurity B = about 0.6, impurity C = about 0.8,
impurity D = about 2.2, impurity E = about 2.6,
Solubility : practically insoluble in water, soluble in dimethyl impurity F = about 4.5.
sulfoxide, practically insoluble in alcohol. It dissolves in dilute
solutions of alkali hydroxides. System suitability : reference solution (c) :
– resolution : minimum of 2.5 between the peaks due to
IDENTIFICATION impurities B and C.
A. Infrared absorption spectrophotometry (2.2.24). Limits :
Comparison : diosmin CRS. – correction factors : for the calculation of contents,
B. Examine the chromatograms obtained in the assay. multiply the peak areas of the following impurities by
Results : the principal peak in the chromatogram obtained the corresponding correction factor : impurity A = 0.38 ;
with the test solution is similar in retention time and size impurity F = 0.61,
to the principal peak in the chromatogram obtained with – impurity A : not more than 0.2 times the area of the
reference solution (a). principal peak in the chromatogram obtained with
reference solution (b) (1 per cent),
TESTS – impurity B : not more than the area of the principal peak
Iodine : maximum 0.1 per cent. in the chromatogram obtained with reference solution (b)
Determine the total content of iodine by potentiometry, using (5 per cent),
an iodide-selective electrode (2.2.36), after oxygen combustion – impurity C : not more than 0.6 times the area of the
(2.5.10). principal peak in the chromatogram obtained with
Test solution. Wrap 0.100 g of the substance to be examined in reference solution (b) (3 per cent),
a piece of filter paper and place it in a sample carrier. Introduce – impurity E : not more than 0.6 times the area of the
into the flask 50 mL of a 0.2 g/L solution of hydrazine R. Flush principal peak in the chromatogram obtained with
the flask with oxygen for 10 min. Ignite the filter paper. Stir reference solution (b) (3 per cent),

2072 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 8.0 Diphenhydramine hydrochloride

– impurity F : not more than 0.6 times the area of the principal
peak in the chromatogram obtained with reference
solution (b) (3 per cent),
– any other impurity : not more than 0.2 times the area of
the principal peak in the chromatogram obtained with
reference solution (b) (1 per cent),
– total of other impurities and impurity A : not more than
0.2 times the area of the principal peak in the chromatogram F. 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-
obtained with reference solution (b) (1 per cent), benzopyran-4-one (diosmetin).
– total : not more than twice the area of the principal peak
in the chromatogram obtained with reference solution (b) 01/2008:0023
(10 per cent), corrected 6.0
– disregard limit : 0.02 times the area of the principal peak
in the chromatogram obtained with reference solution (b)
(0.1 per cent).
DIPHENHYDRAMINE
Heavy metals (2.4.8) : maximum 20 ppm.
HYDROCHLORIDE
2.0 g complies with test C. Prepare the reference solution using
4.0 mL of lead standard solution (10 ppm Pb) R. Diphenhydramini hydrochloridum
Water (2.5.12) : maximum 6.0 per cent, determined on 0.300 g.
Sulfated ash (2.4.14) : maximum 0.2 per cent, determined on
1.0 g.
ASSAY
Liquid chromatography (2.2.29), as described in the test for
related substances.
C17H22ClNO Mr 291.8
Injection : test solution and reference solution (a). [147-24-0]
STORAGE DEFINITION
In an airtight container. 2-(Diphenylmethoxy)-N,N-dimethylethanamine
IMPURITIES hydrochloride.
Content : 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder.
Solubility : very soluble in water, freely soluble in alcohol.
IDENTIFICATION
A. 1-(3-hydroxy-4-methoxyphenyl)ethanone
(acetoisovanillone), First identification : C, D.
Second identification : A, B, D.
A. Melting point (2.2.14) : 168 °C to 172 °C.
B. Dissolve 50 mg in alcohol R and dilute to 100.0 mL with
the same solvent. Examined between 230 nm and 350 nm,
the solution shows 3 absorption maxima (2.2.25), at
253 nm, 258 nm and 264 nm. The ratio of the absorbance
measured at the maximum at 258 nm to that measured
at the maximum at 253 nm is 1.1 to 1.3. The ratio of the
B. (2S)-7-[[6-O-(6-deoxy-α-L-mannopyranosyl)-β-D- absorbance measured at the maximum at 258 nm to that
glucopyranosyl]oxy]-5-hydroxy-2-(3-hydroxy-4- measured at the maximum at 264 nm is 1.2 to 1.4.
methoxyphenyl)-2,3-dihydro-4H-1-benzopyran-4-one C. Infrared absorption spectrophotometry (2.2.24).
(hesperidin),
Preparation : discs.
Comparison : diphenhydramine hydrochloride CRS.
D. It gives the reactions of chlorides (2.3.1).
TESTS
Solution S. Dissolve 1.0 g in carbon dioxide-free water R and
dilute to 20 mL with the same solvent.
Appearance of solution. Solution S and a fivefold dilution of
C. R1 = R3 = H, R2 = OH : 7-[[6-O-(6-deoxy-α-L- solution S are clear (2.2.1). Solution S is not more intensely
mannopyranosyl)-β-D-glucopyranosyl]oxy]-5-hydroxy-2- coloured than reference solution BY6 (2.2.2, Method II).
(4-hydroxyphenyl)-4H-1-benzopyran-4-one (isorhoifolin),
Acidity or alkalinity. To 10 mL of solution S add 0.15 mL of
D. R1 = OH, R2 = OCH3, R3 = I : 7-[[6-O-(6-deoxy-α-L- methyl red solution R and 0.25 mL of 0.01 M hydrochloric acid.
mannopyranosyl)-β-D-glucopyranosyl]oxy]-5-hydroxy-2- The solution is pink. Not more than 0.5 mL of 0.01 M sodium
(3-hydroxy-4-methoxyphenyl)-6-iodo-4H-1-benzopyran- hydroxide is required to change the colour of the indicator
4-one (6-iododiosmin), to yellow.
E. R1 = R3 = H, R2 = OCH3 : 7-[[6-O-(6-deoxy-α-L- Related substances. Liquid chromatography (2.2.29).
mannopyranosyl)-β-D-glucopyranosyl]oxy]-5-hydroxy-2- Test solution. Dissolve 70 mg of the substance to be examined
(4-methoxyphenyl)-4H-1-benzopyran-4-one (linarin), in the mobile phase and dilute to 20.0 mL with the mobile

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