Dexpanthenol EUROPEAN PHARMACOPOEIA 10.

Results : the principal spot in the chromatogram obtained

with the test solution is similar in position, colour and size
to the principal spot in the chromatogram obtained with
the reference solution.
TESTS
Solution S. Dissolve 2.50 g in carbon dioxide-free water R and
C. 9-fluoro-11β,17-dihydroxy-16α-methylpregna-1,4-diene- dilute to 50.0 mL with the same solvent.
3,20-dione (21-deoxydexamethasone).
Appearance of solution. Solution S is clear (2.2.1) and not
more intensely coloured than reference solution B6 (2.2.2,
04/2021:0761 Method II).
pH (2.2.3) : maximum 10.5 for solution S.
Specific optical rotation (2.2.7): + 29.0 to + 32.0 (anhydrous
substance), determined on solution S.
 

DEXPANTHENOL Impurity A and other amino compounds : maximum 1.0 per

cent.
Dexpanthenolum Dissolve 4.000 g in 60 mL of glacial acetic acid R and
immediately titrate with 0.1 M perchloric acid, determining
the end-point potentiometrically (2.2.20).
1 mL of 0.1 M perchloric acid is equivalent to 7.5 mg of
C3H9NO.
Related substances. Liquid chromatography (2.2.29). Protect
C9H19NO4 Mr 205.3 the solutions from light.
[81-13-0]
Buffer solution. A 1.56 g/L solution of sodium dihydrogen
DEFINITION phosphate R previously adjusted to pH 7.0 with phosphoric
(2R)-2,4-Dihydroxy-N-(3-hydroxypropyl)-3,3-dimethyl- acid R.
butanamide. Test solution. Dissolve 0.600 g of the substance to be examined
Content : 98.0 per cent to 101.0 per cent (anhydrous substance). in the buffer solution and dilute to 100.0 mL with the buffer
solution.
CHARACTERS Reference solution (a). Dilute 1.0 mL of the test solution to
Appearance : colourless or slightly yellowish, viscous, 100.0 mL with the buffer solution. Dilute 1.0 mL of this
hygroscopic liquid, or a white or almost white, crystalline solution to 10.0 mL with the buffer solution.
powder. Reference solution (b). Dissolve 3.0 mg of dexpanthenol
Solubility : very soluble in water, freely soluble in ethanol impurity B CRS and 3.0 mg of pantolactone CRS (impurity C)
(96 per cent) and practically insoluble in heptane. in the buffer solution and dilute to 100.0 mL with the buffer
solution.
IDENTIFICATION
Reference solution (c). Mix 1 mL of the test solution and 1 mL
First identification : A, B. of reference solution (b) and dilute to 10 mL with the buffer
Second identification : C. solution.
A. Specific optical rotation (see Tests). Column :
B. Infrared absorption spectrophotometry (2.2.24). – size : l = 0.15 m, Ø = 3.0 mm ;
Preparation : discs prepared as follows if recording in – stationary phase : octadecylsilyl silica gel for
transmission mode : dissolve the substance to be examined chromatography R (3.5 μm);
and the reference substance separately in 1.0 mL of – temperature : 35 °C.
anhydrous ethanol R to obtain a concentration of 5 mg/mL.
Mobile phase :
Place dropwise 0.5 mL of this solution on a disc of
potassium bromide R. Dry the disc at 100-105 °C for – mobile phase A : mix 1 volume of acetonitrile R1 and
15 min. 99 volumes of a 1.56 g/L solution of sodium dihydrogen
phosphate R previously adjusted to pH 2.5 with phosphoric
Comparison : dexpanthenol CRS.
acid R ;
C. Thin-layer chromatography (2.2.27).
– mobile phase B : acetonitrile R1 ;
Test solution. Dissolve 10 mg of the substance to be
examined in a mixture of 0.25 mL of water R and 4 mL of Time Mobile phase A Mobile phase B
methanol R. (min) (per cent V/V) (per cent V/V)
0-6 100 0
Reference solution. Dissolve 10 mg of dexpanthenol CRS in
a mixture of 0.25 mL of water R and 4 mL of methanol R. 6 - 21 100 → 50 0 → 50
Plate : TLC silica gel plate R. 21 - 30 50 50
Mobile phase : glacial acetic acid R, water R, 2-propanol R
(5:15:80 V/V/V). Flow rate : 1.0 mL/min.
Application : 5 μL. Detection : spectrophotometer at 200 nm.
Development : over 4/5 of the plate. Injection : 5 μL.
Drying : in air. Identification of impurities: use the chromatogram obtained
Detection : heat at 120 °C for 20 min ; treat the warm with reference solution (b) to identify the peaks due to
plate with a 3 g/L solution of ninhydrin R in a mixture impurities B and C.
of 3 volumes of glacial acetic acid R and 100 volumes of Relative retention with reference to dexpanthenol
anhydrous ethanol R ; allow to dry and heat again at 120 °C (retention time = about 6 min): impurity B = about 0.4 ;
for a few minutes ; examine in daylight. impurity C = about 0.6.

5464 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.4 Dihydralazine sulfate, hydrated

System suitability : reference solution (c) : 01/2016:1310

– resolution : minimum 2.5 between the peaks due to corrected 10.4
impurities B and C ; minimum 1.5 between the peaks due
to impurity C and dexpanthenol ;
– signal-to-noise ratio : minimum 10 for the peak due to
impurity C.
Calculation of percentage contents : DIHYDRALAZINE SULFATE,
– for impurities B and C, use the concentration of impurity C HYDRATED
in reference solution (b) ;
– for impurities other than B and C, use the concentration of Dihydralazini sulfas hydricus
dexpanthenol in reference solution (a).
Limits :
– impurity C : maximum 1.0 per cent ;
– impurity B : maximum 0.5 per cent ;
– unspecified impurities : for each impurity, maximum
0.10 per cent ;
– total : maximum 2.0 per cent ; C8H12N6O4S,2½H2O Mr 333.3
– reporting threshold : 0.05 per cent. Dihydralazine sulfate, anhydrous : [7327-87-9]
Water (2.5.12): maximum 1.0 per cent, determined on 1.000 g. DEFINITION
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on (Phthalazine-1,4(2H,3H)-diylidene)dihydrazine sulfate
1.0 g. 2.5-hydrate.
Content : 98.0 per cent to 102.0 per cent (dried substance).
ASSAY
To 0.250 g add 50.0 mL of 0.1 M perchloric acid. Boil under CHARACTERS
a reflux condenser for 7 h, protected from humidity. Allow Appearance : white or slightly yellow, crystalline powder.
to cool and transfer quantitatively to a titration vessel using Solubility : slightly soluble in water, practically insoluble in
glacial acetic acid R. Add 50.0 mL of a 9.02 g/L solution of anhydrous ethanol. It dissolves in dilute mineral acids.
sodium acetate R in glacial acetic acid R and titrate with 0.1 M
perchloric acid, determining the end-point potentiometrically IDENTIFICATION
(2.2.20). Carry out a blank titration. A. Infrared absorption spectrophotometry (2.2.24).
1 mL of 0.1 M perchloric acid is equivalent to 20.53 mg Comparison : Ph. Eur. reference spectrum of dihydralazine
of C9H19NO4. sulfate hydrated.
STORAGE B. Dissolve about 50 mg in 5 mL of dilute hydrochloric acid R.
The solution gives reaction (a) of sulfates (2.3.1).
In an airtight container.
TESTS
IMPURITIES
Appearance of solution. The solution is clear (2.2.1) and not
Specified impurities : A, B, C.
more intensely coloured than reference solution BY6 (2.2.2,
Other detectable impurities (the following substances would, Method II).
if present at a sufficient level, be detected by one or other of
Dissolve 0.20 g in dilute nitric acid R and dilute to 10 mL with
the tests in the monograph. They are limited by the general
the same acid.
acceptance criterion for other/unspecified impurities and/or
by the general monograph Substances for pharmaceutical Related substances. Liquid chromatography (2.2.29). Prepare
use (2034). It is therefore not necessary to identify these the solutions immediately before use.
impurities for demonstration of compliance. See also 5.10. Test solution. Dissolve 50.0 mg of the substance to be
Control of impurities in substances for pharmaceutical use) : D. examined in a 6 g/L solution of glacial acetic acid R and dilute
to 50.0 mL with the same solution.
Reference solution (a). Dilute 1.0 mL of the test solution to
A. 3-aminopropan-1-ol, 100.0 mL with the mobile phase containing 0.5 g/L of sodium
edetate R. Dilute 1.0 mL of this solution to 10.0 mL with the
mobile phase containing 0.5 g/L of sodium edetate R.
Reference solution (b). Dilute 1.0 mL of the test solution to
50.0 mL with the mobile phase containing 0.5 g/L of sodium
edetate R.
B. (2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid (pantoic
acid), Reference solution (c). Dissolve 5 mg of dihydralazine for
system suitability CRS in a 6 g/L solution of glacial acetic
acid R and dilute to 5 mL with the same solution.
Column :
– size : l = 0.25 m, Ø = 4.6 mm ;
– stationary phase : base-deactivated end-capped cyanosilyl
silica gel for chromatography R (5 μm).
C. (3R)-3-hydroxy-4,4-dimethyloxolan-2-one (pantolactone),
Mobile phase : mix 22 volumes of acetonitrile for
chromatography R and 78 volumes of a solution containing
1.44 g/L of sodium laurilsulfate R and 0.75 g/L of
tetrabutylammonium bromide R, then adjust to pH 3.0 with
dilute sulfuric acid R1.
D. (5Ξ)-5-(1-hydroxy-2-methylpropan-2-yl)-3-(3- Flow rate : 1.5 mL/min.
hydroxypropyl)-1,3-oxazolidin-4-one. Detection : spectrophotometer at 230 nm.

General Notices (1) apply to all monographs and other texts 5465