JP XVI Official Monographs / Naproxen 1147

(3) To 20 mL of Naphazoline and Chlorpheniramine Flow rate: Adjust the flow rate so that the retention time
Solution add 5 mL of sodium hydroxide TS, extract with 10 of chlorpheniramine is about 10 minutes.
mL of diethyl ether, and separate the diethyl ether layer. Selection of column: Proceed with 10 mL of the standard
Take 5 mL of this solution, distil off the solvent, dissolve the solution under the above operating conditions. Use a column
residue in 5 mL of methanol, and use this solution as the giving well-resolved peaks of the internal standard, naphazo-
sample solution. Separately, dissolve 0.01 g each of napha- line and chlorpheniramine in this order.
zoline nitrate and Chlorpheniramine Maleate RS in 10 mL
Containers and storage Containers—Tight containers.
and 5 mL of methanol, respectively, and use these solutions
Storage—Light-resistant.
as standard solutions (1) and (2). Perform the test with these
solutions as directed under Thin-layer Chromatography
<2.03>. Spot 5 mL each of the sample solution and standard
solutions on a plate of silica gel with fluorescent indicator Naproxen
for thin-layer chromatography. Develop the plate with a
ナプロキセン
mixture of chloroform, methanol, acetone and ammonia so-
lution (28) (73:15:10:2) to a distance of about 10 cm, and air-
dry the plate. Examine under ultraviolet light (main wave-
length: 254 nm): two spots from the sample solution exhibit
the same R f values as the spots from standard solutions (1)
and (2). Spray evenly Dragendorff's TS on the plate: the
C14H14O3: 230.26
spots from standard solutions (1) and (2) and the cor-
(2S )-2-(6-Methoxynaphthalen-2-yl)propanoic acid
responding spot from the sample solutions reveal an orange
[22204-53-1]
color.
Assay Pipet 4 mL of Naphazoline and Chlorpheniramine Naproxen, when dried, contains not less than 98.5z
Solution, add exactly 4 mL of the internal standard solution, of C14H14O3.
then add water to make 10 mL, and use this solution as the
Description Naproxen occurs as white crystals or crystal-
sample solution. Weigh accurately about 50 mg of naphazo-
line powder. It is odorless.
line nitrate for assay, dried at 1059C for 2 hours, and about
It is freely soluble in acetone, soluble in methanol, in
0.1 g of Chlorpheniramine Maleate RS, dried at 1059C for 3
ethanol (99.5) and in chloroform, sparingly soluble in diethyl
hours, dissolve in water to make exactly 100 mL. Pipet 4 mL
ether, and practically insoluble in water.
of this solution, add exactly 4 mL of the internal standard
It dissolves in sodium hydroxide TS.
solution, then add water to make 10 mL, and use this solu-
tion as the standard solution. Perform the test with 10 mL Identification (1) Dissolve 0.01 g of Naproxen in 5 mL of
each of the sample solution and standard solutions as di- methanol, add 5 mL of water, then add 2 mL of potassium
rected under Liquid Chromatography <2.01> according to iodide TS and 5 mL of a solution of potassium iodate (1 in
the following conditions, and calculate the ratios, QTa and 100), and shake: a yellow to yellow-brown color develops.
QTb, of the peak height of naphazoline and chlorphenira- To this solution add 5 mL of chloroform, and shake: a light
mine to that of the internal standard of the sample solution, red-purple color develops in the chloroform layer.
and the ratios, QSa and QSb, of the peak height of naphazo- (2) To 1 mL of a solution of Naproxen in ethanol (99.5)
line and chlorpheniramine to that of the internal standard of (1 in 300) add 4 mL of hydroxylamine perchlorate-dehy-
the standard solution. drated ethanol TS and 1 mL of N, N?-dicyclohexylcarbodii-
mide-dehydrated ethanol TS, shake well, and allow to stand
Amount (mg) of naphazoline nitrate (C14H14N2.HNO3)
in lukewarm water for 20 minutes. After cooling, add 1 mL
＝ MSa × QTa/QSa × 1/25
of iron (III) perchlorate-dehydrated ethanol TS, and shake:
Amount (mg) of chlorpheniramine maleate a red-purple color develops.
(C16H19ClN2.C4H4O4) (3) Determine the absorption spectrum of a solution of
＝ MSb × QTb/QSb × 1/25 Naproxen in ethanol (99.5) (1 in 50,000) as directed under
Ultraviolet-visible Spectrophotometry <2.24>, and compare
MSa: Amount (mg) of naphazoline nitrate for assay
the spectrum with the Reference Spectrum: both spectra
MSb: Amount (mg) of Chlorpheniramine Maleate RS
exhibit similar intensities of absorption at the same wave-
Internal standard solution—A solution of ethenzamide in lengths.
methanol (1 in 1000). (4) Determine the infrared absorption spectrum of
Operating conditions— Naproxen, previously dried, as directed in the potassium
Detector: An ultraviolet absorption photometer (wave- bromide disk method under Infrared Spectrophotometry
length: 254 nm). <2.25>, and compare the spectrum with the Reference Spec-
Column: A stainless steel column, about 4 mm in inside trum: both spectra exhibit similar intensities of absorption at
diameter and 25 to 30 cm in length, packed with octadecyl- the same wave numbers.
silanized silica gel for liquid chromatography (5 mm in parti-
Optical rotation <2.49> [a]25
D : ＋63.0 – ＋68.59(after dry-
cle diameter).
ing, 0.1 g, chloroform, 10 mL, 100 mm).
Column temperature: Room temperature.
Mobile phase: A mixture of acetonitrile and a solution of Melting point <2.60> 154 – 1589
C.
sodium laurylsulfate (1 in 500) in diluted phosphoric acid
Purity (1) Clarity of solution—Dissolve 2.0 g of Napro-
(1 in 1000) (1:1).
xen in 20 mL of acetone: the solution is clear. Perform the
1148 Nateglinide / Official Monographs JP XVI
test with this solution as directed under Ultraviolet-visible
Spectrophotometry <2.24>: the absorbance at 400 nm is not Nateglinide
more than 0.070.
(2) Heavy metals <1.07>—Proceed with 2.0 g of Napro- ナテグリニド
xen 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).
(3) Arsenic <1.11>—Prepare the test solution with 2.0 g
of Naproxen according to Method 3, and perform the test
(not more than 1 ppm).
(4) Related substances—Conduct this procedure without
exposure to daylight, using light-resistant vessels. Dissolve
C19H27NO3: 317.42
0.10 g of Naproxen in 10 mL of a mixture of chloroform and
N-[trans-4-(1-Methylethyl)cyclohexanecarbonyl]-D-phenylalanine
ethanol (99.5) (1:1), and use this solution as the sample solu-
[105816-04-4]
tion. Pipet 2 mL of the sample solution, and add a mixture
of chloroform and ethanol (99.5) (1:1) to make exactly 100
Nateglinide, when dried, contains not less than
mL. Pipet 5 mL of this solution, add a mixture of chlo-
98.0z and not more than 102.0z of C19H27NO3.
roform and ethanol (99.5) (1:1) to make exactly 50 mL, and
use this solution as the standard solution. Perform the test Description Nateglinide occurs as a white crystalline pow-
with these solutions as directed under Thin-layer Chroma- der.
tography <2.03>. Spot 10 mL each of the sample solution and It is freely soluble in methanol and in ethanol (99.5),
standard solution on a plate of silica gel with fluorescent in- sparingly soluble in acetonitrile, and practically insoluble in
dicator for thin-layer chromatography. Develop the plate water.
with a mixture of hexane, dichloromethane, tetrahydrofuran It dissolves in dilute sodium hydroxide TS.
and acetic acid (100) (50:30:17:3) to a distance of about 12
Identification (1) Determine the absorption spectrum of a
cm, and air-dry the plate. Examine under ultraviolet light
solution of Nateglinide in methanol (1 in 1000) as directed
(main wavelength: 254 nm): the spots other than the princi-
under Ultraviolet-visible Spectrophotometry <2.24>, and
pal spot and the spot of the starting point from the sample
compare the spectrum with the Reference Spectrum or the
solution are not more intense than the spot from the stand-
spectrum of a solution of Nateglinide RS prepared in the
ard solution.
same manner as the sample solution: both spectra exhibit
Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, similar intensities of absorption at the same wavelengths.
3 hours). (2) Determine the infrared absorption spectrum of
Nateglinide as directed in the potassium bromide disk
Residue on ignition <2.44> Not more than 0.1z (1 g).
method under Infrared Spectrophotometry <2.25>, and
Assay Weigh accurately about 0.5g of Naproxen, previ- compare the spectrum with the Reference Spectrum or the
ously dried, add 100 mL of diluted methanol (4 in 5), dis- spectrum of Nateglinide RS: both spectra exhibit similar
solve by gentle warming if necessary, and titrate <2.50> with intensities of absorption at the same wave numbers. If any
0.1 mol/L sodium hydroxide VS (indicator: 3 drops of phe- difference appears between the spectra, recrystallize the
nolphthalein TS). Perform a blank determination, and make sample and the reference standard according to the method
any necessary correction. otherwise specified, filter and dry the crystals, and perform
the test with the crystals.
Each mL of 0.1 mol/L sodium hydroxide VS
＝ 23.03 mg of C14H14O3 Optical rotation <2.49> [a]20
D : －36.5 – －40.09(after drying
0.2 g, dilute sodium hydroxide TS, 20 mL, 100 mm).
Containers and storage Containers—Well-closed contain-
ers. Purity (1) Heavy metals <1.07>—Proceed with 2.0 g of
Storage—Light-resistant. Nateglinide 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) Related substances—Dissolve 0.25 g of Nateglinide in
20 mL of acetonitrile. To 4 mL of this solution add the mo-
bile phase to make 25 mL, and use this solution as the sam-
ple solution. Pipet 2.5 mL of the sample solution, and add
the mobile phase to make exactly 50 mL. Pipet 2 mL of this
solution, add the mobile phase to make exactly 100 mL, and
use this solution as the standard solution. Perform the test
with exactly 10 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 nateglinide from the sample solution is
not larger than the peak area of nateglinide from the stand-
ard solution.