Carboplatin

Methane. Gas chromatography (2.2.28).

Gas to be examined. The substance to be examined.
Reference gas. A mixture containing 100 ppm V/V of
methane R in carbon monoxide R.
Column :
material : stainless steel ;
size : l = 2 m, = 4 mm ;
stationary phase : ethylvinylbenzene-divinylbenzene
copolymer R (177-250 m).
Carrier gas : nitrogen for chromatography R.
Flow rate : 10 mL/min.
Temperature :
column : 95 C ;
detector : 240 C.
Detection : ame ionisation.
Injection : 1 mL.
Run time : 3 min.
Retention time : methane = about 1.8 min.
Limit :
methane : not more than the area of the corresponding
peak in the chromatogram obtained with the reference gas
(100 ppm V/V).
Hydrogen. Gas chromatography.
Gas to be examined. The substance to be examined.
Reference gas. A mixture containing 300 ppm V/V of hydrogen
for chromatography R in carbon monoxide R.
Column :
material : stainless steel ;
size : l = 2 m, = 2 mm ;
stationary phase : molecular sieve for chromatography
(149-177 m) with a nominal pore size of 0.5 nm.
Carrier gas : argon for chromatography R.
Flow rate : 30 mL/min.
Temperature :
column : 100 C ;
detector : 160 C.
Detection : thermal conductivity.
Injection : 1 mL.
Run time : 4 min.
Relative retention with reference to carbon monoxide
(retention time = about 2.3 min) : hydrogen = about 0.4.
Limit :
hydrogen : not more than the area of the corresponding
peak in the chromatogram obtained with the reference gas
(300 ppm V/V).
Nickel tetracarbonyl and iron pentacarbonyl : not
detectable, using a detector tube having a limit of detection
of 0.1 ppm V/V (2.1.6).
Water: maximum 10 ppm V/V, determined using an
electrolytic hygrometer (2.5.28).

EUROPEAN PHARMACOPOEIA 8.0

STORAGE
Under pressure in suitable containers complying with the
legal regulations.
IMPURITIES
Specified impurities : A, B, C, D, E, F.
A. CO2 : carbon dioxide,
B. CH4 : methane,
C. H2 : hydrogen,
D. Ni(CO)4 : nickel tetracarbonyl,
E. Fe(CO)5 : iron pentacarbonyl,
F. H2O : water.
07/2009:1081
corrected 7.5

CARBOPLATIN
Carboplatinum

C6H12N2O4Pt
[41575-94-4]

Mr 371.3

DEFINITION
(SP-4-2)-Diammine[cyclobutan-1,1-dicarboxylato(2-)-O,O]platin.
Content : 98.0 per cent to 102.0 per cent (dried substance).
CHARACTERS
Appearance : colourless, crystalline powder.
Solubility : sparingly soluble in water, very slightly soluble in
acetone and in ethanol (96 per cent).
mp : about 200 C, with decomposition.
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison : Ph. Eur. reference spectrum of carboplatin.

TESTS
Solution S. Dissolve 0.25 g in carbon dioxide-free water R and
dilute to 25 mL with the same solvent.
Appearance of solution. Solution S is clear (2.2.1) and
colourless (2.2.2, Method II).
Impurity B and acidity : maximum 0.5 per cent, calculated
as impurity B.
To 10 mL of solution S add 0.1 mL of phenolphthalein
solution R1. The solution is colourless. Not more than 0.7 mL
of 0.01 M sodium hydroxide is required to change the colour
of the indicator to pink.
Related substances. Liquid chromatography (2.2.29).
Test solution. Dissolve 20.0 mg of the substance to be
examined in a mixture of equal volumes of acetonitrile R
ASSAY
and water R and dilute to 20.0 mL with the same mixture of
solvents.
Infrared analyser (2.5.25).
Gas to be examined. The substance to be examined, previously Reference solution. Dilute 0.5 mL of the test solution to
200.0 mL with the mobile phase.
ltered to avoid stray light phenomena.
Column :
Reference gas (a). Carbon monoxide R.
size : l = 0.25 m, = 4.6 mm ;
Reference gas (b). A mixture containing 95.0 per cent V/V of
stationary phase : aminopropylsilyl silica gel for
carbon monoxide R and 5.0 per cent V/V of nitrogen R1.
chromatography R (5 m).
Calibrate the apparatus and set the sensitivity using reference
Mobile
phase : water R, acetonitrile R (13:87 V/V).
gases (a) and (b). Measure the content of carbon monoxide in
Flow rate : 2 mL/min.
the gas to be examined.

1770

See the information section on general monographs (cover pages)

Carboprost trometamol

EUROPEAN PHARMACOPOEIA 8.0

Detection : spectrophotometer at 230 nm.

Injection : 10 L.
Run time : 2.5 times the retention time of carboplatin.
Relative retention with reference to carboplatin (retention
time = about 7 min) : impurity A = about 0.3.
System suitability : test solution :
number of theoretical plates : minimum 5000 ; if necessary,
adjust the concentration of acetonitrile in the mobile phase ;
mass distribution ratio : minimum 4.0 ; if necessary, adjust
the concentration of acetonitrile in the mobile phase ;
symmetry factor : maximum 2.0 ; if necessary, adjust the
concentration of acetonitrile in the mobile phase.
Limits :
impurity A : not more than the area of the principal peak
in the chromatogram obtained with the reference solution
(0.25 per cent) ;
total : not more than twice the area of the principal peak in
the chromatogram obtained with the reference solution
(0.5 per cent) ;
disregard limit : 0.2 times the area of the principal peak in
the chromatogram obtained with the reference solution
(0.05 per cent).
Chlorides (2.4.4): maximum 100 ppm.
Dissolve 0.5 g in water R, heating slightly if necessary, and
dilute to 20 mL with the same solvent. Filter if necessary.
Dilute 10 mL of this solution to 15 mL with water R. Prepare
the standard using 5 mL of chloride standard solution (5 ppm
Cl) R.
Ammonium (2.4.1, Method B) : maximum 100 ppm,
determined on 0.20 g.
Prepare the standard using 0.2 mL of ammonium standard
solution (100 ppm NH4) R.
Silver : maximum 10 ppm.
Inductively coupled plasma-atomic emission spectrometry
(2.2.57).
Test solution. Dissolve 0.50 g in a 1 per cent V/V solution of
nitric acid R and dilute to 50.0 mL with the same solution.
Reference solutions. Prepare the reference solutions using
silver standard solution (5 ppm Ag) R, diluting with a 1 per
cent V/V solution of nitric acid R.
Wavelength : 328.1 nm.
Soluble barium : maximum 10 ppm.
Inductively coupled plasma-atomic emission spectrometry
(2.2.57).
Test solution. Use the solution described in the test for silver.
Reference solutions. Prepare the reference solutions using
barium standard solution (50 ppm Ba) R, diluting with a 1 per
cent V/V solution of nitric acid R.
Wavelength : 455.4 nm.
Loss on drying (2.2.32): maximum 0.5 per cent, determined
on 1.000 g by drying in an oven at 105 C.
ASSAY
Use the residue obtained in the test for loss on drying. Ignite
0.200 g of the residue to constant mass at 800 50 C.
1 mg of the residue is equivalent to 1.903 mg of C6H12N2O4Pt.
STORAGE
Protected from light.
IMPURITIES
Specified impurities : A, B.

A. cis-diamminedichloroplatinum(II) (cisplatin),
General Notices (1) apply to all monographs and other texts

B. cyclobutane-1,1-dicarboxylic acid.
01/2008:1712

CARBOPROST TROMETAMOL
Carboprostum trometamolum

C25H47NO8
[58551-69-2]

Mr 489.7

DEFINITION
2-Amino-2-(hydroxymethyl)propane-1,3-diol
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3hydroxy-3-methyloct-1-enyl]cyclopentyl]hept-5-enoate
((15S)-15-methyl-PGF2).
Content : 94.0 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance : white or almost white powder.
Solubility : soluble in water.
IDENTIFICATION
A. Specic optical rotation (see Tests).
B. Infrared absorption spectrophotometry (2.2.24).
Comparison : Ph. Eur. reference spectrum of carboprost
trometamol.
TESTS
Specic optical rotation (2.2.7) : + 18 to + 24 (anhydrous
substance).
Dissolve 0.100 g in ethanol (96 per cent) R and dilute to
10.0 mL with the same solvent.
Related substances. Liquid chromatography (2.2.29).
Test solution. Dissolve 15.0 mg of the substance to be
examined in a mixture of 23 volumes of acetonitrile R and
77 volumes of water for chromatography R and dilute to
10.0 mL with the same mixture of solvents.
Reference solution (a). Dissolve 15.0 mg of carboprost
trometamol CRS (containing impurity A) in a mixture of
23 volumes of acetonitrile R and 77 volumes of water for
chromatography R and dilute to 10.0 mL with the same
mixture of solvents.
Reference solution (b). Dilute 1.0 mL of reference solution (a)
and 0.15 mL of (15R)-15-methylprostaglandin F2 R
(impurity B) to 100.0 mL with a mixture of 23 volumes of
acetonitrile R and 77 volumes of water for chromatography R.
Reference solution (c). Dilute 2.0 mL of the test solution to
20.0 mL with a mixture of 23 volumes of acetonitrile R and
77 volumes of water for chromatography R. Dilute 2.0 mL
of this solution to 20.0 mL with a mixture of 23 volumes of
acetonitrile R and 77 volumes of water for chromatography R.
Column :
size : l = 0.15 m, = 4.6 mm,
stationary phase : octadecylsilyl silica gel for
chromatography R1 (5 m) with a pore size of
8-10 nm and a carbon loading of 12-19 per cent.
Mobile phase : mix 23 volumes of acetonitrile R1 and
77 volumes of a 2.44 g/L solution of sodium dihydrogen
phosphate R in water for chromatography R previously adjusted
to pH 2.5 with phosphoric acid R.

1771