KP X 543
of solution B before injection of the test solution and
the standard solution, and keep re-equilibrium.
Mobile phase A: Mix 0.6 mL of phosphoric acid
with 100 mL of water.
Mobile phase B: Mix 0.6 mL of phosphoric acid
with 100 mL of acetonitrile.
Flow rate: 1 mL/min.
System suitability
System performance: Dissolve suitable amount
each of Etodolac Related Substance I RS and Etodolac
RS in acetonitrile to make solutions containing 10 μg
of Etodolac Related Substance I RS and 0.2 mg of
Etodolac RS per mL, respectively. When the procedure
is run with 20 μL of this solution, as directed under the
above operating conditions, etodolac related substance
I and Etodolac are eluted in this order with the resolu-
tion between their peaks being not less than 3.0.
System repeatability: When the test is repeated 6
times with 20 µL each of the solution for system per-
formance, as directed under the above operating condi-
tions, the relative standard deviation of the ratio of the
peak area is not more than 3 %.
Water Not more than 0.5 % (2 g, volumetric titration,
direct titration).
Residue on Ignition Not more than 0.1 % (1 g).
Assay Weigh accurately about 0.23 g of Etodolac,
dissolve in 60 mL of methanol, and titrate with 0.1
mol/L tetrabutylammonium hydroxide VS (potentiom-
etric titration, Endpoint Detection Method in
Titrimetry). Perform a blank determination, and make
any necessary correction.
Each mL of 0.1 mol/L tetrabutylammonium
hydroxide VS = 28.736 mg of C17H21NO3
Containers and Storage Containers—Tight con-
tainers.
Etodolac Tablets
Etodolac Tablets contain not less than 90.0 % and not
more than 110.0 % of the labeled amount of etodolac
(C17H21NO3: 287.36)
Method of Preparation Prepare as directed under
Tablets, with Etodolac.
Identification Test The retention time of major peak
of the test solution corresponds to that of the standard
solution as obtained in the Assay.
Dissolution Test Take 1 tablet of Etodolac Tablets,
perform the test as directed in Method 1 under the Dis-
solution Test at 100 revolutions per minute, and using
1000 mL of pH 6.8 phosphate buffer as the dissolution
solution. After 30 minutes from starting of the test, take
20 mL of the dissolved solution, and filter through a
membrane filter with a pore size of 0.8 μm or less.
Discard the first 10 mL of the filtrate, and use the sub-
sequent filtrate as the test solution. Seperately weigh
accurately 25 mg of Etodolac RS, and dissolve in the
dissolution solution to make exactly 100 mL. Pipet 5
mL of this solution, add the dissolution solution to
make exactly 50 mL, and use this solution as the stand-
ard solution. Determine the absorbances, AT and AS, of
the test solution and the standard solution, respectively,
at the maximum wavelength at about 274 nm as di-
rected under Ultraviolet-visible Spectrophotometry
using the dissolution solution as a blank. The dissolu-
tion rate of Etodolac Tablets after 30 minutes should be
not less than 80 %.
Dissolution rate (%) with respect to the labeled amount
A 100
of etodolac (C17H21NO3) = WS × T ×
AS C
WS: Amount (mg) of Etodolac RS
C: Labeled amount (mg) of etodolac (C17H21NO3)
in 1 tablet.
Uniformity of Dosage Units It meets the require-
ment when the content uniformity test is performed
according to the following method.
Take 1 tablet of Etodolac Tablets, and shake with 10
mL of phosphate buffer until the tablet is disintegrated.
Add phosphate buffer to make exactly 100 mL, and
centrifuge this solution. Pipet x mL of the supernatant
liquid, add phosphate buffer to make exactly v mL to
provide a solution that contains about 25 μg of
etodolac (C17H21NO3) per mL, and use this solution as
the test solution. Separately, weigh accurately 25 mg of
etodolac reference standard, and dissolve in phosphate
buffer to make exactly 100 mL. Pipet 10 mL of this
solution, add phosphate buffer to make exactly 100 mL,
and use this solution as the standard solution. Deter-
mine the absorbances, AT and AS, of the test solution
and the standard solution, respectively, at maximum
wavelength at about 274 nm as directed under the Ul-
traviolet-visible spectrophotometry.
Amount (mg) of etodolac (C17 H 21 NO 3 )
AT V 1
= amount (mg) of Etodolac RS × × ×
AS 10 x
Assay Weigh accurately and powder not less than 20
Etodolac Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.1 g of etodolac
(C17H21NO3), and add 30 mL of a mobile phase. Shake
for 15 minutes, and sonicate 5 minutes for integration.
After cooling, add the mobile phase to make exactly 50
mL. After leaving 10 minutes, pipet 10.0 mL of this
solution, then add the mobile phase to make exactly
100 mL, filter, and use this filtrate as the test solution.
Separately, weigh exactly 20 mg Etodolac RS and dis-
solve in the mobile phase to make exactly 100 mL, and
544 Monographs, Part I

use this solution as the standard solution. Perform the [33419-42-0]

test with 10 μL each of the test solution and the stand-
ard solution as directed under Liquid Chromatography Etoposide contains not less than 98.0 % and not more
according to the following conditions. Determine the than 102.0 % of etoposide (C29H32O13), calculated on
peak areas, AT and AS, of each solution. the anhydrous basis.

Amount (mg) of etodolac (C17 H 21NO3 ) Description Etoposide appears as white crystals or
AT crystalline powder.
= amount (mg) of Etodolac RS × ×5 Etoposide is sparingly soluble in methanol, slightly
AS soluble in ethanol (99.5), and very slightly in water.
Melting point—about 260ºC
Operating conditions
Detector: An ultraviolet absorption photometer Identification (1) Determine the absorption spectra
(wavelength: 274 nm). of solutions of Etoposide and Etoposide RS, respec-
Column: A stainless steel column, about 4.6 nm in tively, in methanol (1 in 10000) as directed under Ul-
internal diameter and about 25 cm in length, packed traviolet-visible Spectrophotometry: both spectra ex-
with 3 ~ 10 μm in particle diameter octadecylsilanized hibit similar intensities of absorption at the same wave-
silicagel for liquid chromatography. lengths.
Mobile phase: acetonitrile ⋅ water ⋅ phosphate mix- (2) Determine the infrared spectra of Etoposide and
ture (500 : 500 : 0.25). Etoposide RS, according to the paste method under
Flow rate: 1.5 mL/minute. Infrared Spectrophotometry, respectively: both spectra
System suitability exhibit similar intensities of absorption at the same
System performance: Dissolve Etodolac related wavenumbers.
substance Ⅰ RS and Etodolac RS in acetonitrile to
make Etodolac related substance Ⅰ RS 10 μg and Specific Optical Rotation [α ] 20 D : −100 ~ −105°
Etodolac RS about 0.2 mg per mL. When the precedure [0.1 g calculated on the anhydrous basis, methanol, 20
is run with 20 μL of this solution, as directed under the mL, 100 mm].
above operating conditions, Etodolac related substance
Ⅰ and Etodolac are eluted in this order with the reso- Purity (1) Heavy metals⎯Proceed with 2.0 g of
lution between their peaks being not less than 3.0. Etoposide according to Method 2 and perform the test.
System repeatability: When the test is repeated 6 Prepare the control solution with 2.0 mL of standard
times with 20 μL each of the standard solution, as di- lead solution (not more than 10 ppm).
rected under the above operating conditions, the rela- (2) Related substances⎯Dissolve 50 mg of
tive standard deviation of the peak areas is not more Etoposide in 10 mL of methanol and add mobile solu-
than 3 %. tion to make 50 mL and use this solution as the test
solution. Pipet 2 mL of the test solution, add the mobile
Containers and Storage Containers—Tight con- phase to make 200 mL, and use this solution as the
tainers. standard solution. Perform the test with exactly 50 μL
each of the test solution and standard solution as di-
rected under Liquid Chromatography according to the
following conditions, and determine each peak area by
Etoposide the automatic integration method: the area of any peak
O other than etoposide obtained with the test solution is
H 3CO
O
not greater than 1/5 times the peak area of etoposide
H H
obtained with the standard solution, and the total area
of all peaks other than the peak of etoposide obtained
HO O O
O with the test solution is not larger than 1/2 times the
CH 3 peak area of etoposide obtained with the standard solu-
H 3CO
HO O
H
tion.
OH
O O Operating conditions
Detector, column, column temperature, mobile
phase, and flow rate: Proceed as directed in the operat-
C29H32O13: 588.56 ing conditions in the Assay.
System suitability
(5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8- Test for the required detectability: Measure ex-
Dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano actly 1 mL of the standard solution, and add the mobile
[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5- phase to make exactly 10 mL. Confirm that the peak
dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H- area of etoposide obtained with 50 μL of this solution
[2]benzofuro[6,5-f][1,3]benzodioxol-8-one is equivalent to 7 to 13 % of that of etoposide obtained