Isoxsuprine hydrochloride EUROPEAN PHARMACOPOEIA 11.

Resolution (2.2.25): minimum 1.7 for the absorbance ratio.

Specific absorbance at the absorption maxima :
– at 269 nm : 71 to 74 ;
– at 275 nm : 70 to 73.
H. (2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-3- B. Infrared absorption spectrophotometry (2.2.24).
oxocyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
(13-cis-4-oxoretinoic acid), Preparation : discs.
Comparison : isoxsuprine hydrochloride CRS.
If the spectra obtained show differences, dissolve 50 mg
of the substance to be examined and of the reference
substance separately in 2 mL of methanol R, add 15 mL of
methylene chloride R, evaporate to dryness and record new
spectra using the residues.
C. Thin-layer chromatography (2.2.27).
I. (2Z,4E,6E,8E)-9-[(3RS)-3-hydroxy-2,6,6-
trimethylcyclohex-1-en-1-yl]-3,7-dimethylnona- Test solution. Dissolve 20 mg of the substance to be
2,4,6,8-tetraenoic acid (13-cis-4-hydroxyretinoic acid). examined in methanol R and dilute to 10 mL with the same
solvent.
Reference solution. Dissolve 20 mg of isoxsuprine
hydrochloride CRS in methanol R and dilute to 10 mL with
the same solvent.
01/2017:1119
corrected 10.0 Plate : TLC silica gel G plate R.
Mobile phase : concentrated ammonia R, methanol R,
methylene chloride R (0.25:15:85 V/V/V).
Application : 10 μL.
Development : over a path of 12 cm.
ISOXSUPRINE HYDROCHLORIDE
Drying : in a current of warm air.
Isoxsuprini hydrochloridum Detection : spray with a 10 g/L solution of potassium
permanganate R.
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.
D. To 1 mL of solution S (see Tests) add 0.05 mL of copper
C18H24ClNO3 Mr 337.8 sulfate solution R and 0.5 mL of strong sodium hydroxide
[579-56-6] solution R. The solution becomes blue. Add 1 mL of ether R
and shake. Allow to separate. The upper layer remains
DEFINITION colourless.
(1RS,2SR)-1-(4-Hydroxyphenyl)-2-[[(1SR)-1-methyl-2- E. 2 mL of solution S gives reaction (a) of chlorides (2.3.1).
phenoxyethyl]amino]propan-1-ol hydrochloride.
Content : 99.0 per cent to 101.0 per cent (dried substance). TESTS
Solution S. Dissolve 0.50 g, with gentle heating if necessary,
CHARACTERS in carbon dioxide-free water R, cool and dilute to 50.0 mL with
Appearance : white or almost white, crystalline powder. the same solvent.
Solubility : sparingly soluble in water and in ethanol (96 per Appearance of solution. Solution S is clear (2.2.1) and
cent), practically insoluble in methylene chloride. colourless (2.2.2, Method II).
mp : about 205 °C, with decomposition. pH (2.2.3): 4.5 to 6.0 for solution S.
Optical rotation (2.2.7) : − 0.05° to + 0.05°, determined on
IDENTIFICATION solution S.
First identification : B, E. Phenones : maximum 1.0 per cent, calculated as impurity B.
Second identification : A, C, D, E. Dissolve 10.0 mg in water R and dilute to 100.0 mL with
the same solvent. The absorbance (2.2.25) of the solution
A. Ultraviolet and visible absorption spectrophotometry measured at the absorption maximum at 310 nm is not greater
(2.2.25). than 0.10.
Test solution. Dissolve 50.0 mg in 0.1 M hydrochloric acid Related substances. Gas chromatography (2.2.28). Prepare
and dilute to 50.0 mL with the same acid. Dilute 10.0 mL the solutions immediately before use.
of this solution to 100.0 mL with 0.1 M hydrochloric acid.
Internal standard solution (a). Dissolve 0.1 g of hexacosane R
Spectral range : 230-350 nm.
in trimethylpentane R and dilute to 20 mL with the same
Absorption maxima : at 269 nm and 275 nm. solvent.

3150 See the information section on general monographs (cover pages)

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EUROPEAN PHARMACOPOEIA 11.0 Isradipine

Internal standard solution (b). Dilute 1 mL of internal 1 mL of 0.1 M sodium hydroxide is equivalent to 33.78 mg
standard solution (a) to 50 mL with trimethylpentane R. of C18H24ClNO3.
Test solution. To 10.0 mg of the substance to be examined,
STORAGE
add 0.5 mL of N-trimethylsilylimidazole R. Heat to 65 °C
for 10 min. Allow to cool, then add 2.0 mL of the internal Protected from light.
standard solution (b) and 2.0 mL of water R. Shake. Use the
upper layer. IMPURITIES
Reference solution (a). To 10.0 mg of the substance to be Specified impurities : B.
examined, add 0.5 mL of N-trimethylsilylimidazole R. Heat Other detectable impurities (the following substances would,
to 65 °C for 10 min. Allow to cool, then add 2.0 mL of if present at a sufficient level, be detected by one or other of
the internal standard solution (a) and 2.0 mL of water R. the tests in the monograph. They are limited by the general
Shake. Dilute 1.0 mL of the upper layer to 50.0 mL with acceptance criterion for other/unspecified impurities and/or
trimethylpentane R. by the general monograph Substances for pharmaceutical
Reference solution (b). To 10.0 mg of the substance to be use (2034). It is therefore not necessary to identify these
examined, add 0.5 mL of N-trimethylsilylimidazole R. Heat impurities for demonstration of compliance. See also 5.10.
to 65 °C for 10 min. Allow to cool, then add 2.0 mL of Control of impurities in substances for pharmaceutical use) : A.
trimethylpentane R and 2.0 mL of water R. Shake. Use the
upper layer.
Column :
– material : glass ;
– size : l = 1.5 m, Ø = 4 mm ;
– stationary phase : silanised diatomaceous earth for gas A. (1RS,2SR)-1-(4-hydroxyphenyl)-2-[[(1RS)-1-methyl-2-
chromatography R (125-135 μm) impregnated with 3 per phenoxyethyl]amino]propan-1-ol,
cent m/m of methylpolysiloxane R.
Carrier gas : nitrogen for chromatography R.
Flow rate : 30 mL/min.
Temperature :
Time Temperature
(min) (°C) B. 1-(4-hydroxyphenyl)-2-[(1-methyl-2-
Column 0 - 25 195
phenoxyethyl)amino]propan-1-one.

25 - 29 195 → 215

29 - 39 215
01/2023:2110
Injection port 225

Detector 225

Detection : flame ionisation.

Injection : 1 μL. ISRADIPINE
Elution order : isoxsuprine, hexacosane.
System suitability : Isradipinum
– resolution : minimum 5.0 between the peaks due to
isoxsurpine and hexacosane in the chromatogram obtained
with reference solution (a);
– in the chromatogram obtained with reference solution (b),
there is no peak with the same retention time as the internal
standard.
Limit :
– total : calculate the ratio (R) of the area of the peak due
to the trimethylsilyl derivative of isoxsuprine to the
C19H21N3O5 Mr 371.4
area of the peak due to the internal standard from the
[75695-93-1]
chromatogram obtained with reference solution (a); from
the chromatogram obtained with the test solution, calculate DEFINITION
the ratio of the sum of the areas of any peaks, apart from the
3-Methyl 5-(propan-2-yl) (4RS)-4-(2,1,3-benzoxadiazol-4-yl)-
principal peak and the peak due to the internal standard,
to the area of the peak due to the internal standard : this 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.
ratio is not greater than R (2.0 per cent). Content : 97.0 per cent to 102.0 per cent (dried substance).
Loss on drying (2.2.32) : maximum 0.5 per cent, determined CHARACTERS
on 1.000 g by drying in an oven at 105 °C.
Appearance : yellow, crystalline powder.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on Solubility : practically insoluble in water, freely soluble in
1.0 g. acetone, soluble in methanol.
ASSAY mp : about 168 °C.
Dissolve 0.250 g in 80 mL of ethanol (96 per cent) R and add IDENTIFICATION
1.0 mL of 0.1 M hydrochloric acid. Carry out a potentiometric
titration (2.2.20), using 0.1 M sodium hydroxide. Read Infrared absorption spectrophotometry (2.2.24).
the volume added between the 2 points of inflexion. Comparison : isradipine CRS.

General Notices (1) apply to all monographs and other texts 3151
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