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CHARACTERS
Appearance : white or almost white, hygroscopic, crystalline
powder.
Solubility : slightly soluble in water, freely soluble in
dimethylformamide, very slightly soluble in anhydrous
ethanol.
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison : fludarabine phosphate CRS.
TESTS
Appearance of solution. The solution is clear (2.2.1) and not
more intensely coloured than reference solution BY5 (2.2.2,
Method II).
Dissolve 50 mg in 5.0 mL of dimethylformamide R with the
ASSAY
aid of ultrasound.
Dissolve 0.100 g in 40 mL of anhydrous acetic acid R and add Specic optical rotation (2.2.7) : + 10.0 to + 14.0 (anhydrous
100 mL of acetic anhydride R. Titrate with 0.1 M perchloric
substance).
acid determining the end-point potentiometrically (2.2.20).
Dissolve 0.100 g in water R with the aid of ultrasound and
1 mL of 0.1 M perchloric acid is equivalent to 12.91 mg
dilute to 20.0 mL with the same solvent.
of C4H4FN3O.
Related substances. Liquid chromatography (2.2.29) : use the
normalisation procedure. Prepare the solutions immediately
STORAGE
before use.
Protected from light.
Test solution. Dissolve 20 mg of the substance to be examined
in 50 mL of water R with the aid of ultrasound and dilute to
IMPURITIES
100.0 mL with the same solvent.
Specified impurities : A, B.
Reference solution (a). Dissolve 20 mg of fludarabine
phosphate CRS in 50 mL of water R with the aid of ultrasound
and dilute to 100.0 mL with the same solvent.
Reference solution (b). Dissolve 20 mg of the substance to be
examined in 20 mL of 0.1 M hydrochloric acid with the aid of
ultrasound. Heat in a water-bath at 80 C for 15 min, cool to
room temperature, mix and dilute to 100.0 mL with water R.
A. 5-uoropyrimidine-2,4(1H,3H)-dione (uorouracil),
Reference solution (c). Dilute 1.0 mL of reference solution (a)
to 100.0 mL with water R. Dilute 1.0 mL of this solution to
20.0 mL with water R.
Reference solution (d). Dissolve 5 mg of fludarabine for system
suitability CRS (containing impurities D, E and F) in 10 mL
of water R with the aid of ultrasound and dilute to 25.0 mL
with the same solvent.
B. 2-ethoxy-5-uoropyrimidin-4(3H)-one.
Blank solution : 0.02 M hydrochloric acid.
A. Early eluting impurities.
Column :
size : l = 0.15 m, = 4.6 mm ;
04/2013:1781
stationary phase : end-capped octadecylsilyl silica gel for
chromatography R (5 m).
FLUDARABINE PHOSPHATE
Mobile phase : mix 60 volumes of methanol R and
940 volumes of a 1.36 g/L solution of potassium dihydrogen
Fludarabini phosphas
phosphate R.
Flow rate : 1 mL/min.
Detection : spectrophotometer at 260 nm and at 292 nm.
Injection : 10 L of the test solution and reference
solutions (a), (b) and (c).
Run time : 4.5 times the retention time of the principal peak
in the chromatogram obtained with the test solution.
Identification of impurities: use the chromatogram
obtained with reference solution (b) at 292 nm to identify
the peaks due to impurities A and B, the response at
C10H13FN5O7P
Mr 365.2
292 nm being much higher than at 260 nm ; use the
[75607-67-9]
chromatogram supplied with fludarabine phosphate CRS
and the chromatogram obtained with reference solution (a)
DEFINITION
at 260 nm to identify impurity C.
2-Fluoro-9-(5-O-phosphono--D-arabinofuranosyl)-9HRelative retention with reference to udarabine phosphate
purin-6-amine.
(retention time = about 9 min): impurity A = about 0.26 ;
impurity B = about 0.34 ; impurity C = about 0.42.
Content : 97.0 per cent to 102.0 per cent (anhydrous substance).
2248
Fludarabine phosphate
A. 6-amino-9-(5-O-phosphono--D-arabinofuranosyl)-9Hpurin-2-ol,
B. 6-amino-7H-purin-2-ol,
C. 9-(3,5-di-O-phosphono--D-arabinofuranosyl)-2-uoro9H-purin-6-amine,
D. 2-uoro-7H-purin-6-amine,
2249
Fludrocortisone acetate
01/2008:0767
corrected 8.0
FLUDROCORTISONE ACETATE
Fludrocortisoni acetas
E. 9--D-arabinofuranosyl-2-uoro-9H-purin-6-amine,
C23H31FO6
[514-36-3]
F. 2-ethoxy-9-(5-O-phosphono--D-arabinofuranosyl)-9Hpurin-6-amine,
G. 9-(2-chloro-2-deoxy-5-O-phosphono--Darabinofuranosyl)-2-uoro-9H-purin-6-amine,
H. 9-(2,5-anhydro--D-arabinofuranosyl)-2-uoro-9H-purin6-amine,
I. 9-(5-O-phosphono--D-arabinofuranosyl)-9H-purine-2,6diamine,
J. 2-methoxy-9-(5-O-phosphono--D-arabinofuranosyl)-9Hpurin-6-amine.
2250
Mr 422.5
DEFINITION
9-Fluoro-11,17-dihydroxy-3,20-dioxopregn-4-en-21-yl
acetate.
Content : 97.0 per cent to 103.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder.
Solubility : practically insoluble in water, sparingly soluble in
anhydrous ethanol.
IDENTIFICATION
First identification : A, B.
Second identification : C, D, E.
A. Infrared absorption spectrophotometry (2.2.24).
Comparison : fludrocortisone acetate CRS.
If the spectra obtained in the solid state show differences,
dissolve the substance to be examined and the reference
substance separately in the minimum volume of acetone R,
evaporate to dryness and record new spectra using the
residues.
B. Thin-layer chromatography (2.2.27).
Solvent mixture : methanol R, methylene chloride R
(1:9 V/V).
Test solution. Dissolve 10 mg of the substance to be
examined in the solvent mixture and dilute to 10 mL with
the solvent mixture.
Reference solution (a). Dissolve 10 mg of fludrocortisone
acetate CRS in the solvent mixture and dilute to 10 mL
with the solvent mixture.
Reference solution (b). Dissolve 5 mg of cortisone
acetate CRS in 5 mL of reference solution (a).
Plate : TLC silica gel F254 plate R.
Mobile phase : add a mixture of 1.2 volumes of water R and
8 volumes of methanol R to a mixture of 15 volumes of
ether R and 77 volumes of methylene chloride R.
Application : 5 L.
Development : over a path of 15 cm.
Drying : in air.
Detection A : examine in ultraviolet light at 254 nm.
Results A : the principal spot in the chromatogram obtained
with the test solution is similar in position and size to
the principal spot in the chromatogram obtained with
reference solution (a).
Detection B : spray with alcoholic solution of sulfuric acid R.
Heat at 120 C for 10 min or until the spots appear. Allow to
cool. Examine in daylight and in ultraviolet light at 365 nm.
Results B : the principal spot in the chromatogram obtained
with the test solution is similar in position, colour in
daylight, uorescence in ultraviolet light at 365 nm and
size to the principal spot in the chromatogram obtained
with reference solution (a).
See the information section on general monographs (cover pages)