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474

Cefuroxime Axetil / Ocial Monographs

10 mL each of these solutions as directed under Liquid Chromatography <2.01> according to the following conditions,
and calculate the ratios, QT and QS, of the peak area of
ceftriaxone to that of the internal standard.
Amount [mg (potency)] of ceftriaxone (C18H18N8O7S3)
WS (QT/QS) 1000

WS: Amount [mg (potency)] of Ceftriaxone Sodium Reference Standard


Internal standard solutionA solution of diethyl terephthalate in a mixture of water and acetonitrile for liquid chromatography (11:9) (9 in 5000).
Operating conditions
Detector: An ultraviolet absorption photometer (wavelength: 254 nm).
Column: A stainless steel column 4.6 mm in inside diameter and 25 cm in length, packed with octadecylsilanized
silica gel for liquid chromatography (10 mm in particle
diameter).
Column temperature: A constant temperature of about
259C.
Mobile phase: Dissolve 5.796 g of anhydrous disodium
hydrogen phosphate and 3.522 g of potassium dihydrogen
phosphate in water to make exactly 1000 mL, and use this solution as solution A. Dissolve 20.256 g of citric acid monohydrate and 7.840 g of sodium hydroxide in water to make exactly 1000 mL, and use this solution as solution B. Dissolve
4.00 g of tetra-n-heptylammonium bromide in 450 mL of
acetonitrile for liquid chromatography, and add 490 mL of
water, 55 mL of solution A, and 5 mL of solution B.
Flow rate: Adjust the ow rate so that the retention time of
ceftriaxone is about 7 minutes.
System suitability
System performance: When the procedure is run with
10 mL of the standard solution under the above operating
conditions, ceftriaxone and the internal standard are eluted
in this order with the resolution between these peaks being
not less than 6.
System repeatability: When the test is repeated 6 times with
10 mL of the standard solution under the above operating
conditions, the relative standard deviation of the ratios of the
peak area of ceftriaxone to that of the internal standard is not
more than 1.0z.
Containers and storage ContainersTight containers.
StorageLight-resistant.

Cefuroxime Axetil

C20H22N4O10S: 510.47
(1RS)-1-Acetoxyethyl (6R,7R)-3-carbamoyloxymethyl-7[(Z)-2-furan-2-yl-2-(methoxyimino)acetylamino]-8-oxo-5-

JP XV
thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
[64544-07-6]

Cefuroxime Axetil contains not less than 800 mg


(potency) and not more than 850 mg (potency) per mg,
calculated on the anhydrous basis and corrected by
the amount of acetone. The potency of Cefuroxime
Axetil is expressed as mass (potency) of cefuroxime
(C16H16N4O8S: 424.39).
Description Cefuroxime Axetil occurs as white to yellowish
white, non-crystalline powder.
It is freely soluble in dimethylsulfoxide, soluble in
methanol, sparingly soluble in ethanol (95), and very slightly
soluble in water.
Identication (1) Determine the absorption spectrum of a
solution of Cefuroxime Axetil in methanol (3 in 200,000) as
directed under Ultraviolet-visible Spectrophotometry <2.24>,
and compare the spectrum with the Reference Spectrum or
the spectrum of a solution of Cefuroxime Axetil Reference
Standard prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at
the same wavelengths.
(2) Determine the infrared absorption spectrum of
Cefuroxime Axetil as directed in the potassium bromide disk
method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Cefuroxime Axetil Reference Standard: both spectra
exhibit similar intensities of absorption at the same wave
numbers.
(3) Determine the spectrum of a solution of Cefuroxime
Axetil in deuterated dimethylsulfoxide for nuclear magnetic
resonance spectroscopy (1 in 20) as directed under Nuclear
Magnetic Resonance Spectroscopy <2.21> (1H), using
tetramethylsilane for nuclear magnetic resonance spectroscopy as an internal reference compound: it exhibits a
double signal or a pair of double signals A at around
d 1.5 ppm, a pair of single signals B at around d 2.1 ppm, and
a single signal C at around d 3.9 ppm. The ratio of the integrated intensity of each signal, A:B:C, is about 1:1:1.
Optical rotation <2.49> [a]20
D : 41 479(0.5 g, methanol,
50 mL, 100 mm).
Purity (1) Heavy metals <1.07>Proceed with 2.0 g of
Cefuroxime Axetil according to Method 2, and perform the
test. Prepare the control solution with 2.0 mL of Standard
Lead Solution (not more than 10 ppm).
(2) Arsenic <1.11>Put 1.0 g of Cefuroxime Axetil in a
crucible, add 10 mL of a solution of magnesium nitrate hexahydrate in ethanol (95) (1 in 10), burn the ethanol, then heat
gradually to incinerate. If a carbonized substance remains,
moisten with a small amount of nitric acid, and ignite to incinerate. Cool, add 10 mL of dilute hydrochloric acid to the
residue, dissolve by warming on a water bath, and perform
the test using this solution as the test solution (not more than
2 ppm).
(3) Related substanceDissolve 25 mg of Cefuroxime
Axetil in 4 mL of methanol, add a solution of ammonium dihydrogen phosphate (23 in 1000) to make 10 mL, and use this
solution as the sample solution. Pipet 1 mL of the sample solution, add 40 mL of methanol and a solution of ammonium
dihydrogen phosphate (23 in 1000) to make exactly 100 mL,
and use this solution as the standard solution. Perform the

JP XV
test with exactly 2 mL each of the sample solution and standard solution as directed under Liquid Chromatography
<2.01> according to the following conditions, and determine
each peak area by the automatic integration method: the area
of the peak other than cefuroxime axetil obtained from the
sample solution is not more than 1.5 times the sum area of
two peaks of cefuroxime axetil obtained from the standard
solution, and the sum area of the peaks other than
cefuroxime axetil from the sample solution is not more than 4
times the sum area of two peaks of cefuroxime axetil from
the standard solution.
Operating conditions
Detector, column, column temperature, mobile phase, and
ow rate: Proceed as directed in the operating conditions in
the Assay.
Time span of measurement: About 3 times as long as the
retention time of the peak having the larger retention time of
the two peaks of cefuroxime axetil beginning after the solvent
peak.
System suitability
Test for required detectability: Measure exactly 1 mL of
the standard solution, and add 4 mL of methanol and a solution of ammonium dihydrogen phosphate (23 in 1000) to
make exactly 10 mL. Conrm that the sum area of the two
peaks of cefuroxime axetil obtained from 2 mL of this solution is equivalent to 7 to 13z of that obtained from 2 mL of
the standard solution.
System performance: Proceed as directed in the system
suitability in the Assay.
System repeatability: When the test is repeated 6 times with
2 mL of the standard solution under the above operating conditions, the relative standard deviation of the sum area of the
two peaks of cefuroxime axetil is not more than 2.0z.
(4) AcetoneWeigh accurately about 1 g of Cefuroxime
Axetil, add exactly 0.2 mL of the internal standard solution
and dimethylsulfoxide to make exactly 10 mL, and use this
solution as the sample solution. Separately, weigh accurately
about 0.5 g of acetone, and add dimethylsulfoxide to make
exactly 100 mL. Pipet 0.2 mL of this solution, add exactly 0.2
mL of the internal standard solution and dimethylsulfoxide
to make exactly 10 mL, and use this solution as the standard
solution. Perform the test with 1 mL each of the sample solution and standard solution as directed under Gas Chromatography <2.02> according to the following conditions, determine each peak area by the automatic integration method,
and calculate the ratios, QT and QS, of the peak area of acetone to that of the internal standard: the amount of acetone is
not more than 1.3z.
Amount (z) of acetone (WS/WT) (QT/QS) 0.2

WS: Amount (g) of acetone


WT: Amount (g) of the sample
Internal standard solutionA solution of 1-propanol in
dimethylsulfoxide (1 in 200).
Operating conditions
Detector: A hydrogen ame-ionization detector.
Column: A glass column 3 mm in inside diameter and 2 m
in length, packed with siliceous earth for gas chromatography coated with a mixture of polyethylene glycol 600 for
gas chromatography and polyethylene glycol 1500 for gas
chromatography (1:1) in the ratio of 20z (125 150 mm in
particle diameter).

Ocial Monographs / Cefuroxime Axetil

475

Column temperature: A constant temperature of about


909C.
Temperature of injection port: A constant temperature of
about 1159
C.
Carrier gas: Nitrogen
Flow rate: Adjust the ow rate so that the retention time of
the internal standard is about 4 minutes.
System suitability
System performance: When the procedure is run with 1 mL
of the standard solution under the above operating conditions, acetone and the internal standard are eluted in this order with the resolution between these peaks being not less than
5.
System repeatability: When the test is repeated 6 times with
1 mL of the standard solution under the above operating conditions, the relative standard deviation of the ratios of the
peak area of acetone to that of the internal standard is not
more than 5.0z.
Water <2.48> Not more than 2.0z (0.4 g, volumetric titration, direct titration).
Residue on ignition <2.44>

Not more than 0.2z (0.5 g).

Isomer ratio Perform the test with 10 mL of the sample solution obtained in the Assay as directed under Liquid Chromatography <2.01> according to the following conditions,
and determine the area, Aa, of the peak having the smaller
retention time and the area, Ab, of the peak having the bigger
retention time of the two peaks of cefuroxime axetil:
Ab/(Aa Ab) is between 0.48 and 0.55.
Operating conditions
Detector, column, column temperature, mobile phase, and
ow rate: Proceed as directed in the operating conditions in
the Assay.
System suitability
System performance, and system repeatability: Proceed as
directed in the system suitability in the Assay.
Assay Weigh accurately an amount of Cefuroxime Axetil
and Cefuroxime Axetil Reference Standard, equivalent to
about 50 mg (potency), and dissolve each in methanol to
make exactly 50 mL. Pipet 10 mL each of these solutions,
add exactly 5 mL of the internal standard solution, 5 mL of
methanol and a solution of ammonium dihydrogen phosphate (23 in 1000) to make 50 mL, and use these solutions as
the sample solution and the standard solution. Perform the
test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01>
according to the following conditions, and determine the
ratios, QT and QS, of the sum area of the two peaks of
cefuroxime axetil to the peak area of the internal standard.
Amount [mg (potency)] of cefuroxime (C16H16N4O8S)
WS (QT/QS) 1000

WS: Amount [mg (potency)] of Cefuroxime Axetil Reference Standard


Internal standard solutionA solution of acetanilide in
methanol (27 in 5000).
Operating conditions
Detector: An ultraviolet absorption photometer (wavelength: 278 nm).
Column: A stainless steel column 4.6 mm in inside diameter and 20 cm in length, packed with trimethylsilanized

476

Cefuroxime Sodium / Ocial Monographs

silica gel for liquid chromatography (5 mm in particle diameter).


Column temperature: A constant temperature of about
259C.
Mobile phase: A mixture of a solution of ammonium
dihydrogen phosphate (23 in 1000) and methanol (5:3).
Flow rate: Adjust the ow rate so that the retention time of
the peak having the smaller retention time of the two peaks of
cefuroxime axetil is about 8 minutes.
System suitability
System performance: When the procedure is run with
10 mL of the standard solution under the above operating
conditions, the internal standard and cefuroxime axetil are
eluted in this order with the resolution between the two peaks
of cefuroxime axetil being not less than 1.5.
System repeatability: When the test is repeated 6 times with
10 mL of the standard solution under the above operating
conditions, the relative standard deviation of the ratios of the
sum area of the two peaks of cefuroxime axetil to the peak
area of the internal standard is not more than 1.0z.
Containers and storage ContainersTight containers.
StorageLight-resistant.

Cefuroxime Sodium

C16H15N4NaO8S: 446.37
Monosodium (6 R,7 R )-3-carbamoyloxymethyl-7-[( Z )-2furan-2-yl-2-(methoxyimino)acetylamino]-8-oxo-5-thia-1azabicyclo[4.2.0]oct-2-ene-2-carboxylate [56238-63-2 ]

Cefuroxime Sodium contains not less than 875 mg


(potency) per mg, calculated on the anhydrous basis.
The potency of Cefuroxime Sodium is expressed as
mass (potency) of cefuroxime (C16H16N4O8S: 424.39).
Description Cefuroxime Sodium occurs as a white to light
yellowish white, crystals or crystalline powder.
It is freely soluble in water, soluble in methanol, and very
slightly soluble in ethanol (95).
Identication (1) Determine the absorption spectrum of a
solution of Cefuroxime Sodium (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefuroxime Sodium Reference Standard prepared in the same manner as sample solution: both
spectra exhibit similar intensities of absorption at the same
wavelengths.
(2) Determine the infrared absorption spectrum of
Cefuroxime Sodium as directed in the potassium bromide
disk method under Infrared Spectrophotometry <2.25>, and
compare the spectrum with the Reference Spectrum or the
spectrum of Cefuroxime Sodium Reference Standard: both
spectra exhibit similar intensities of absorption at the same

JP XV
wave numbers.
(3) Determine the spectrum of a solution of Cefuroxime
Sodium in heavy water for nuclear magnetic resonance spectroscopy (1 in 10) as directed under Nuclear Magnetic
Resonance Spectroscopy <2.21> (1H), using sodium 3trimethylsilylpropanesulfonate
for
nuclear
magnetic
resonance spectroscopy as an internal reference compound: it
exhibits a single signal A at around d 4.0 ppm, a quartet signal B at around d 6.6 ppm, and double signals, C and D, at
around d 6.9 ppm and around d 7.7 ppm, respectively. The
ratio of integrated intensity of each signal, A:B:C:D, is about
3:1:1:1.
(4) Cefuroxime Sodium responds to the Qualitative Tests
<1.09> (1) for sodium salt.
Optical rotation <2.49> [a]20
D : 59 669(0.5 g calculated
on the anhydrous bases, water, 100 mL, 100 mm).
pH <2.54> Dissolve 1.0 g of Cefuroxime Sodium in 10 mL
of water: the pH of the solution is between 6.0 and 8.5.
Purity (1) Clarity and color of solutionDissolve 1.0 g of
Cefuroxime Sodium in 10 mL of water: the solution is clear,
and its absorbance <2.24> at 450 nm is not more than 0.25.
(2) Heavy metals < 1.07 > Proceed with 1.0 g of
Cefuroxime Sodium according to Method 2, and perform the
test. Prepare the control solution with 3.0 mL of Standard
Lead Solution (not more than 30 ppm).
(3) Arsenic <1.11>Prepare the test solution with 1.0 g
of Cefuroxime Sodium according to Method 3, and perform
the test (not more than 2 ppm).
(4) Related substancesDissolve 25 mg of Cefuroxime
Sodium in 25 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to
make exactly 100 mL, and use this solution as the standard
solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid
Chromatography <2.01> according to the following conditions, and calculate the areas of each peak by the automatic
integration method: each peak area other than cefuroxime
from the sample solution is not more than the peak area of
cefuroxime from the standard solution, and the total of the
peak areas other than cefuroxime from the sample solution is
not more than 3 times of the peak area of cefuroxime from
the standard solution.
Operating conditions
Detector, column, column temperature, mobile phase, and
ow rate: Proceed as directed in the operating conditions in
the Assay.
Time span of measurement: About 4 times as long as the
retention time of cefuroxime beginning after the solvent
peak.
System suitability
Test for required detection: Pipet 1 mL of the standard solution, add water to make exactly 10 mL, and conrm that
the peak area of cefuroxime obtained from 20 mL of this solution is equivalent to 7 to 13z of that of cefuroxime obtained
from 20 mL of the standard solution.
System performance: Proceed as directed in the system
suitability in the Assay.
System repeatability: When the test is repeated 6 times with
20 mL of the standard solution under the above operating
conditions, the relative standard deviation of the peak areas
of cefuroxime is not more than 2.0z.