Ferrous sulfate heptahydrate

EUROPEAN PHARMACOPOEIA 8.0

Wavelength : 232.0 nm.

Atomisation device : air-acetylene ame.
Zinc : maximum 100 ppm.
Atomic absorption spectrometry (2.2.23, Method II).
Test solution. Solution S.
Reference solutions. Prepare the reference solutions using zinc
standard solution (100 ppm Zn) R, diluted as necessary with a
5 per cent V/V solution of lead-free nitric acid R.
Source : zinc hollow-cathode lamp using a transmission band
preferably of 1 nm.
Wavelength : 213.9 nm.
Atomisation device : air-acetylene ame.
ASSAY
Dissolve 2.5 g of sodium hydrogen carbonate R in a mixture
of 150 mL of water R and 10 mL of sulfuric acid R. When
the effervescence ceases, add to the solution 0.140 g of the
substance to be examined and dissolve with gentle shaking.
Add 0.1 mL of ferroin R and titrate with 0.1 M ammonium
and cerium nitrate until the red colour disappears.
1 mL of 0.1 M ammonium and cerium nitrate is equivalent
to 15.19 mg of FeSO4.
STORAGE
In an airtight container.
01/2010:0083
corrected 7.2

FERROUS SULFATE HEPTAHYDRATE

Ferrosi sulfas heptahydricus
FeSO4,7H2O
[7782-63-0]

Mr 278.0

DEFINITION
Content : 98.0 per cent to 105.0 per cent.
CHARACTERS
Appearance : light green, crystalline powder or bluish-green
crystals, eforescent in air.
Solubility : freely soluble in water, very soluble in boiling water,
practically insoluble in ethanol (96 per cent).
Ferrous sulfate heptahydrate is oxidised in moist air, becoming
brown.
IDENTIFICATION
A. It gives the reactions of sulfates (2.3.1).
B. It gives reaction (a) of iron (2.3.1).
C. It complies with the limits of the assay.
TESTS
Solution S. Dissolve 4.0 g in a 5 per cent V/V solution of
lead-free nitric acid R and dilute to 100.0 mL with the same
solution.
pH (2.2.3) : 3.0 to 4.0.
Dissolve 1.0 g in carbon dioxide-free water R and dilute to
20 mL with the same solvent.
Chlorides (2.4.4): maximum 200 ppm.
Dilute 5 mL of solution S to 10 mL with water R and add 5 mL
of dilute nitric acid R. Prepare the standard with a mixture
of 2 mL of water R, 5 mL of dilute nitric acid R and 8 mL of
chloride standard solution (5 ppm Cl) R. Use 0.15 mL of silver
nitrate solution R2 in this test.
Chromium : maximum 50 ppm.
Atomic absorption spectrometry (2.2.23, Method II).
Test solution. Solution S.
General Notices (1) apply to all monographs and other texts

Reference solutions. Prepare the reference solutions using

chromium standard solution (100 ppm Cr) R, diluting with a
5 per cent V/V solution of lead-free nitric acid R.
Source : chromium hollow-cathode lamp using a transmission
band preferably of 1 nm.
Wavelength : 357.9 nm.
Atomisation device : air-acetylene ame.
Copper : maximum 50 ppm.
Atomic absorption spectrometry (2.2.23, Method II).
Test solution. Solution S.
Reference solutions. Prepare the reference solutions using
copper standard solution (0.1 per cent Cu) R, diluting with a
5 per cent V/V solution of lead-free nitric acid R.
Source : copper hollow-cathode lamp using a transmission
band preferably of 1 nm.
Wavelength : 324.7 nm.
Atomisation device : air-acetylene ame.
Ferric ions : maximum 0.3 per cent.
In a ground-glass-stoppered ask, dissolve 5.00 g in a mixture
of 10 mL of hydrochloric acid R and 100 mL of carbon
dioxide-free water R. Add 3 g of potassium iodide R, close the
ask and allow to stand in the dark for 5 min. Titrate the
liberated iodine with 0.1 M sodium thiosulfate, using 0.5 mL
of starch solution R, added towards the end of the titration, as
indicator. Carry out a blank test in the same conditions. Not
more than 2.7 mL of 0.1 M sodium thiosulfate is used, taking
into account the blank titration.
Manganese : maximum 0.1 per cent.
Atomic absorption spectrometry (2.2.23, Method II).
Test solution. Dilute 1.0 mL of solution S to 20.0 mL with a
5 per cent V/V solution of lead-free nitric acid R.
Reference solutions. Prepare the reference solutions using
manganese standard solution (1000 ppm Mn) R, diluting with
a 5 per cent V/V solution of lead-free nitric acid R.
Source : manganese hollow-cathode lamp using a transmission
band preferably of 1 nm.
Wavelength : 279.5 nm.
Atomisation device : air-acetylene ame.
Nickel : maximum 50 ppm.
Atomic absorption spectrometry (2.2.23, Method II).
Test solution. Solution S.
Reference solutions. Prepare the reference solutions using
nickel standard solution (10 ppm Ni) R, diluting with a 5 per
cent V/V solution of lead-free nitric acid R.
Source : nickel hollow-cathode lamp using a transmission band
preferably of 1 nm.
Wavelength : 232.0 nm.
Atomisation device : air-acetylene ame.
Zinc : maximum 50 ppm.
Atomic absorption spectrometry (2.2.23, Method II).
Test solution. Solution S.
Reference solutions. Prepare the reference solutions using
zinc standard solution (100 ppm Zn) R, diluting with a 5 per
cent V/V solution of lead-free nitric acid R.
Source : zinc hollow-cathode lamp using a transmission band
preferably of 1 nm.
Wavelength : 213.9 nm.
Atomisation device : air-acetylene ame.
ASSAY
Dissolve 2.5 g of sodium hydrogen carbonate R in a mixture
of 150 mL of water R and 10 mL of sulfuric acid R. When
the effervescence ceases add to the solution 0.500 g of the
substance to be examined and dissolve with gentle swirling.
Add 0.1 mL of ferroin R and titrate with 0.1 M ammonium
and cerium nitrate until the red colour disappears.

2229

Fexofenadine hydrochloride

EUROPEAN PHARMACOPOEIA 8.0

1 mL of 0.1 M ammonium and cerium nitrate is equivalent

to 27.80 mg of FeSO4,7H2O.
STORAGE
In an airtight container.
01/2008:2280

FEXOFENADINE HYDROCHLORIDE
Fexofenadini hydrochloridum

C32H40ClNO4
[153439-40-8]

Mr 538.1

DEFINITION
2-[4-[(1RS)-1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid
hydrochloride.
Content : 98.0 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance : white or almost white powder.
Solubility : slightly soluble in water, freely soluble in methanol,
very slightly soluble in acetone.
It shows polymorphism (5.9).
IDENTIFICATION
A. Infrared absorption spectrophotometry (2.2.24).
Comparison : fexofenadine hydrochloride CRS.
It the spectra obtained in the solid state show differences,
dissolve the substance to be examined and the reference
substance separately in methanol R, evaporate to dryness
and record new spectra using the residues.
B. Dissolve 30 mg of the substance to be examined in a
mixture of equal volumes of methanol R and water R ;
sonicate if necessary and dilute to 2 mL with the same
mixture of solvents. The solution gives reaction (a) of
chlorides (2.3.1).
TESTS
Impurity B. Liquid chromatography (2.2.29).
Test solution. Dissolve 50.0 mg of the substance to be
examined in the mobile phase and dilute to 100.0 mL with
the mobile phase.
Reference solution (a). Dissolve the contents of a vial of
fexofenadine impurity B CRS in the test solution and dilute to
2.0 mL with the test solution.
Reference solution (b). Dilute 1.0 mL of the test solution to
100.0 mL with the mobile phase. Dilute 1.0 mL of this solution
to 10.0 mL with the mobile phase.
Column :
size : l = 0.25 m, = 4.6 mm ;
stationary phase : silica gel BC for chiral chromatography R1
(5 m).
Mobile phase : mix 20 volumes of acetonitrile for
chromatography R and 80 volumes of a buffer solution
prepared as follows : to 1.15 mL of glacial acetic acid R add
water for chromatography R, adjust to pH 4.0 0.1 with
dilute ammonia R1 and dilute to 1000 mL with water for
chromatography R.
Flow rate : 0.5 mL/min.

2230

Detection : spectrophotometer at 220 nm.

Injection : 20 L.
Run time : 1.2 times the retention time of fexofenadine.
Relative retention with reference to fexofenadine (retention
time = about 20 min): impurity B = about 0.7.
System suitability : reference solution (a) :
resolution : minimum 3.0 between the peaks due to
fexofenadine and impurity B.
Limits :
correction factor : for the calculation of content, multiply
the peak area of impurity B by 1.3 ;
impurity B : not more than the area of the principal peak
in the chromatogram obtained with reference solution (b)
(0.1 per cent).
Related substances. Liquid chromatography (2.2.29).
Buffer solution. Dissolve 6.64 g of sodium dihydrogen
phosphate monohydrate R and 0.84 g of sodium perchlorate R
in water for chromatography R, adjust to pH 2.0 0.1 with
phosphoric acid R and dilute to 1000 mL with water for
chromatography R.
Solvent mixture. Mix equal volumes of acetonitrile for
chromatography R and the buffer solution.
Test solution (a). Dissolve 25.0 mg of the substance to be
examined in 25.0 mL of the solvent mixture.
Test solution (b). Dilute 3.0 mL of test solution (a) to 50.0 mL
with the mobile phase.
Reference solution (a). Dissolve 25.0 mg of fexofenadine
hydrochloride CRS in the solvent mixture and dilute to 25.0 mL
with the solvent mixture. Dilute 3.0 mL of this solution to
50.0 mL with the mobile phase.
Reference solution (b). Dilute 1.0 mL of test solution (a) to
100.0 mL with the mobile phase. Dilute 1.0 mL of this solution
to 10.0 mL with the mobile phase.
Reference solution (c). Dissolve 1 mg each of fexofenadine
impurity A CRS and fexofenadine impurity C CRS in 20 mL of
reference solution (a) and dilute to 200.0 mL with the mobile
phase.
Column :
size : l = 0.25 m, = 4.6 mm ;
stationary phase : phenylsilyl silica gel for chromatography R
(5 m).
Mobile phase : mix 350 volumes of acetonitrile for
chromatography R and 650 volumes of the buffer solution ; add
3 volumes of triethylamine R and mix.
Flow rate : 1.5 mL/min.
Detection : spectrophotometer at 220 nm.
Injection : 20 L of test solution (a) and reference solutions (b)
and (c).
Relative retention with reference to fexofenadine
(retention time = about 9 min) : impurity A = about 1.7 ;
impurity D = about 2.3 ; impurity C = about 3.2.
Run time : 6 times the retention time of fexofenadine for test
solution (a) and reference solution (c), twice the retention
time of fexofenadine for reference solution (b).
System suitability : reference solution (c) :
resolution : minimum 10 between the peaks due to
fexofenadine and impurity A.
Limits :
correction factor : for the calculation of content, multiply
the peak area of impurity A by 1.4 ;
impurities A, C, D : not more than the area of the principal
peak in the chromatogram obtained with reference
solution (b) (0.1 per cent) ;
unspecified impurities : for each impurity, not more than the
area of the principal peak in the chromatogram obtained
with reference solution (b) (0.10 per cent) ;
See the information section on general monographs (cover pages)