FEXOFENADINE HYDROCHLORIDE
Fexofenadini hydrochloridum
C32H40ClNO4
Mr 538.1
[153439-40-8]
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.
If 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 R
(5 μm).
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.

Detection :spectrophotometer at 220 nm.
Injection:20 μL.
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 offexofenadine
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 offexofenadine
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 μm).
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 μL 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) ;
total:not more than 3 times the area of the principal peak
in the chromatogram obtained with reference solution (b)
(0.3 per cent) ;
– disregard limit:0.5 times the area of the principal peak in
the chromatogram obtained with reference solution (b)
(0.05 per cent).
Water (2.5.32): maximum 0.5 per cent.
Dissolve 1.000 g in anhydrous methanol R and dilute to 5.0 mL
with the same solvent. Use 1.0 mL of this solution.
Sulfated ash (2.4.14): maximum 0.1 per cent, determined on
1.0 g.
ASSAY
Liquid chromatography (2.2.29)as described in the test for
related substances with the following modi?cations.
Injection:test solution (b) and reference solution (a).
Run time :twice the retention time of fexofenadine.
Calculate the percentage content of fexofenadine
hydrochloride from the declared content offexofenadine
hydrochloride CRS.
IMPURITIES
Specified impurities : A, B, C, D.
Other detectable impurities (the following substances would,
if present at a suf?cient level, be detected by one or other of
the tests in the monograph. They are limited by the general
acceptance criterion for other/unspeci?ed 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):E, F, G.