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Etidronate disodium
01/2008:1778 ASSAY
corrected 8.3 Dissolve 0.100 g in 2 mL of anhydrous formic acid R and
dilute to 50 mL with glacial acetic acid R. Titrate with 0.1 M
perchloric acid, determining the end-point potentiometrically
ETIDRONATE DISODIUM
(2.2.20).
1 mL of 0.1 M perchloric acid is equivalent to 12.50 mg
Dinatrii etidronas
of C2H6Na2O7P2.
STORAGE
In an airtight container.
C2H6Na2O7P2
[7414-83-7]
IMPURITIES
Specified impurities : A, B.
Mr 250.0
A. H3PO4 : phosphoric acid,
B. H3PO3 : phosphorous acid.
DEFINITION
Disodium dihydrogen (1-hydroxyethylidene)bisphosphonate.
Content : 98.0 per cent to 102.0 per cent (anhydrous substance).
01/2015:0823
ETOPOSIDE
CHARACTERS
Appearance : white or yellowish, hygroscopic powder.
Solubility : freely soluble in water, practically insoluble in
acetone and in ethanol (96 per cent).
Etoposidum
IDENTIFICATION
A. Infrared absorption spectrophotometry (2.2.24).
Comparison : etidronate disodium CRS.
The transmittance at about 2000 cm 1 (5 m) is not less
than 40 per cent without compensation.
B. It gives reaction (a) of sodium (2.3.1).
TESTS
pH (2.2.3) : 4.2 to 5.2.
Dissolve 1.0 g in carbon dioxide-free water R and dilute to
100 mL with the same solvent.
Impurities A and B. Liquid chromatography (2.2.29).
Test solution. Dissolve 20.0 mg of the substance to be
examined in water R and dilute to 10.0 mL with the same
solvent.
Reference solution. To 2.0 mL of a 0.3 g/L solution of
phosphoric acid R add 2.0 mL of a 0.25 g/L solution of
phosphorous acid R and dilute to 50.0 mL with water R.
Column :
size : l = 0.15 m, = 4.6 mm ;
stationary phase : anion-exchange resin R (5 m) ;
temperature : 35 C.
Mobile phase : mix 0.2 mL of anhydrous formic acid R and
1000 mL of water R ; adjust to pH 3.5 with an 80 g/L solution
of sodium hydroxide R.
Flow rate : 1.0 mL/min.
Detection : differential refractometer.
Injection : 100 L.
System suitability : reference solution :
resolution : minimum 2.5 between the peaks due to
impurity A and impurity B.
Limits :
impurities A, B : for each impurity, not more than the area
of the corresponding peak in the chromatogram obtained
with the reference solution (0.5 per cent).
Heavy metals (2.4.8) : maximum 20 ppm.
1.0 g complies with test F. Prepare the reference solution using
2 mL of lead standard solution (10 ppm Pb) R.
Water (2.5.32): maximum 5.0 per cent.
Dissolve 50.0 mg in a mixture of equal volumes of anhydrous
acetic acid R and formamide R and dilute to 5.0 mL with the
same mixture of solvents. Use 1.0 mL of the solution.
4306
C29H32O13
[33419-42-0]
Mr 588.6
DEFINITION
(5R,5aR,8aR,9S)-9-[[4,6-O-[(R)-Ethylidene]--Dglucopyranosyl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol6(5aH)-one.
Content : 98.0 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance : white or almost white, crystalline powder, slightly
hygroscopic.
Solubility : practically insoluble in water, sparingly soluble
in methanol, slightly soluble in ethanol 96 per cent and in
methylene chloride.
IDENTIFICATION
First identification : A, B.
Second identification : C, D.
A. Specic optical rotation (see Tests).
B. Infrared absorption spectrophotometry (2.2.24).
Comparison : etoposide CRS.
C. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 10 mg of the substance to be
examined in a mixture of 1 volume of methanol R and
9 volumes of methylene chloride R and dilute to 2 mL with
the same mixture of solvents.
Reference solution. Dissolve 10 mg of etoposide CRS in
a mixture of 1 volume of methanol R and 9 volumes of
methylene chloride R and dilute to 2 mL with the same
mixture of solvents.
Plate : silica gel H R as the coating substance.
Mobile phase : water R, glacial acetic acid R, acetone R,
methylene chloride R (1.5:8:20:100 V/V/V/V).
Application : 5 L as bands of 10 mm.
Development : immediately, over 6/7 of the plate.
Drying : in a current of warm air for 5 min.
See the information section on general monographs (cover pages)
Etoposide
4307
Etoposide
F. (5R,5aR,8aR,9S)-9-[[4,6-O-[(R)-ethylidene]--Dglucopyranosyl]oxy]-5-[4-[(phenoxyacetyl)oxy]3,5-dimethoxyphenyl]-5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one
(4-phenoxyacetyletoposide),
A. (5R,5aR,8aR,9S)-5-[4-[[(benzyloxy)carbonyl]oxy]-3,5dimethoxyphenyl]-9-[[4,6-O-[(R)-ethylidene]--Dglucopyranosyl]oxy]-5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4-carbobenzoyloxyethylidene-lignan P),
C. (5R,5aR,8aR,9S)-9-[[4,6-O-[(R)-ethylidene]--Dglucopyranosyl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol6(5aH)-one (-etoposide),
E. (5R,5aR,8aR,9S)-9-hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4-desmethylepipodophyllotoxin),
4308
H. (5R,5aR,8aR,9S)-9-ethoxy-5-(4-hydroxy-3,5dimethoxyphenyl)-5,8,8a,9-tetrahydroisobenzofuro-[5,6f][1,3]benzodioxol-6(5aH)-one (4-O-desmethyl-1-Oethylepipodophyllotoxin),
J. (5R,5aR,8aR,9S)-5-(4-hydroxy-3,5-dimethoxyphenyl)9-methoxy-5,8,8a,9-tetrahydroisobenzofuro-[5,6f][1,3]benzodioxol-6(5aH)-one (4-O-desmethyl-1-Omethylepipodophyllotoxin),
See the information section on general monographs (cover pages)
Etoposide
K. 9,9-oxybis[(5R,5aR,8aR,9S)-5-(4-hydroxy-3,5dimethoxyphenyl)-5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one] (di-4-Odesmethylepipodophyllotoxin),
O. (5R,5aR,8aR,9S)-9-[[2,3-bis-O-(dichloroacetyl)-4,6-O-[(S)ethylidene]--L-glucopyranosyl]oxy]-5-(4-hydroxy-3,5dimethoxyphenyl)-5,8,8a,9-tetrahydroisobenzofuro[5,6f][1,3]benzodioxol-6(5aH)-one,
L. (5R,5aR,8aR,9R)-9-hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one (4-O-desmethylpodophyllotoxin),
P. 9-hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)isobenzofuro[5,6-f][1,3]benzodioxol-6(8H)-one,
M. (5R,5aR,8aR,9R)-9-hydroxy-5-(3,4,5-trimethoxyphenyl)5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol6(5aH)-one (podophyllotoxin),
Q. 5-(4-hydroxy-3,5-dimethoxyphenyl)isobenzofuro[5,6f][1,3]benzodioxol-6(8H)-one,
N. (5R,5aR,8aR,9S)-9-[[4,6-O-[(R)-ethylidene]-D-glucopyranosyl]oxy]-5-[4-[[(5R,5aR,8aR,9S)5-(4-hydroxy-3,5-dimethoxyphenyl)-6-oxo5,5a,6,8,8a,9-hexahydroisobenzofuro[5,6f][1,3]benzodioxol-9-yl]oxy]3,5-dimethoxyphenyl]5,8,8a,9-tetrahydroisobenzofuro-[5,6-f][1,3]benzodioxol6(5aH)-one.
R. (5R,5aR,8aR,9S)-9-[[4,6-O-[(R)-ethylidene]--Dglucopyranosyl]oxy]-5-[4-[[(5R,5aR,8aR,9R)-5-(4hydroxy-3,5-dimethoxyphenyl)-6-oxo-5,5a,6,8,8a,9hexahydroisobenzofuro[5,6-f][1,3]benzodioxol9-yl]oxy]-3,5-dimethoxyphenyl]-5,8,8a,9tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol6(5aH)-one.
4309