908 Naphazoline Nitrate / O‹cial Monographs JP XV

＝ 24.67 mg of C14H14N2.HCl ＝ 27.33 mg of C14H14N2.HNO3

Containers and storage Containers—Tight containers. Containers and storage Containers—Tight containers.
Storage—Light-resistant. Storage—Light-resistant.

Naphazoline Nitrate Naproxen

ナファゾリン硝酸塩 ナプロキセン

C14H14O3: 230.26
C14H14N2.HNO3: 273.29 (2S )-2-(6-Methoxynaphthalen-2-yl)propanoic acid
2-(Naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole [22204-53-1 ]
mononitrate [5144-52-5 ]
Naproxen, when dried, contains not less than 98.5z
Naphazoline Nitrate, when dried, contains not less of C14H14O3.
than 98.5z of C14H14N2.HNO3. Description Naproxen occurs as white crystals or crystalline
Description Naphazoline Nitrate occurs as a white, crystal- powder. It is odorless.
line powder. It is odorless, and has a bitter taste. It is freely soluble in acetone, soluble in methanol, in
It is freely soluble in acetic acid (100), soluble in ethanol ethanol (99.5) and in chloroform, sparingly soluble in diethyl
(95), sparingly soluble in water, slightly soluble in acetic an- ether, and practically insoluble in water.
hydride, and practically insoluble in diethyl ether. It dissolves in sodium hydroxide TS.

Identiˆcation (1) To 10 mL of a solution of Naphazoline Identiˆcation (1) Dissolve 0.01 g of Naproxen in 5 mL of

Nitrate (1 in 100) add 5 mL of bromine TS, and boil: a deep methanol, add 5 mL of water, then add 2 mL of potassium
purple color develops. iodide TS and 5 mL of a solution of potassium iodate (1 in
(2) To 20 mL of a solution of Naphazoline Nitrate (1 in 100), and shake: a yellow to yellow-brown color develops. To
100) add 5 mL of sodium hydroxide TS, and extract with two this solution add 5 mL of chloroform, and shake: a light red-
25-mL portions of diethyl ether. Combine the diethyl ether purple color develops in the chloroform layer.
extracts, evaporate to dryness with the aid of a current of air, (2) To 1 mL of a solution of Naproxen in ethanol (99.5)
and dry the residue at 809 C for 1 hour: the residue so ob- (1 in 300) add 4 mL of hydroxylamine perchlorate-dehydrat-
tained melts <2.60> between 1179C and 1209 C. ed ethanol TS and 1 mL of N, N ?-dicyclohexylcarbodiimide-
(3) A solution of Naphazoline Nitrate (1 in 20) responds dehydrated ethanol TS, shake well, and allow to stand in
to the Qualitative Tests <1.09> for nitrate. lukewarm water for 20 minutes. After cooling, add 1 mL of
iron (III) perchlorate-dehydrated ethanol TS, and shake: a
pH <2.54> Dissolve 0.1 g of Naphazoline Nitrate in 10 mL red-purple color develops.
of freshly boiled and cooled water: the pH of the solution is (3) Determine the absorption spectrum of a solution of
between 5.0 and 7.0. Naproxen in ethanol (99.5) (1 in 50,000) as directed under
Melting point <2.60> 167 – 1709
C Ultraviolet-visible Spectrophotometry <2.24>, and compare
the spectrum with the Reference Spectrum: both spectra ex-
Purity (1) Clarity and color of solution—Dissolve 0.5 g of hibit similar intensities of absorption at the same
Naphazoline Nitrate in 50 mL of water: the solution is clear wavelengths.
and colorless. (4) Determine the infrared absorption spectrum of
(2) Heavy metals < 1.07 > —Proceed with 1.0 g of Naproxen, previously dried, as directed in the potassium
Naphazoline Nitrate according to Method 2, and perform the bromide disk method under Infrared Spectrophotometry
test. Prepare the control solution with 2.0 mL of Standard <2.25>, and compare the spectrum with the Reference Spec-
Lead Solution (not more than 20 ppm). trum: both spectra exhibit similar intensities of absorption at
Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, the same wave numbers.
2 hours). Optical rotation <2.49> [a]25 D: ＋63.0 – ＋68.59 (after
Residue on ignition <2.44> Not more than 0.1z (1 g). drying, 0.1 g, chloroform, 10 mL, 100 mm).

Assay Weigh accurately about 0.4 g of Naphazoline Ni- Melting point <2.60> 154 – 1589
C
trate, previously dried, dissolve in 10 mL of acetic acid (100) Purity (1) Clarity of solution—Dissolve 2.0 g of Naprox-
and 40 mL of acetic anhydride, and titrate <2.50> with 0.1 en in 20 mL of acetone: the solution is clear. Perform the test
mol W L perchloric acid VS (indicator: 3 drops of crystal violet with this solution as directed under Ultraviolet-visible Spec-
TS). Perform a blank determination, and make any necessary trophotometry <2.24>: the absorbance at 400 nm is not more
correction. than 0.070.
Each mL of 0.1 mol W
L perchloric acid VS (2) Heavy metals <1.07>—Proceed with 2.0 g of Naprox-
JP XV O‹cial Monographs / Neostigmine Methylsulfate 909

en according to Method 2, and perform the test. Prepare the crystalline powder.
control solution with 2.0 mL of Standard Lead Solution (not It is very soluble in water, and freely soluble in acetonitrile
more than 10 ppm). and in ethanol (95).
(3) Arsenic <1.11>—Prepare the test solution with 2.0 g
Identiˆcation (1) Determine the absorption spectrum of a
of Naproxen according to Method 3, and perform the test
solution of Neostigmine Methylsulfate (1 in 2000) as directed
(not more than 1 ppm).
under Ultraviolet-visible Spectrophotometry <2.24>, and
(4) Related substances—Conduct this procedure without
compare the spectrum with the Reference Spectrum or the
exposure to daylight, using light-resistant vessels. Dissolve
spectrum of Neostigmine Methylsulfate Reference Standard:
0.10 g of Naproxen in 10 mL of a mixture of chloroform and
both spectra exhibit similar intensities of absorption at the
ethanol (99.5) (1:1), and use this solution as the sample solu-
same wavelengths.
tion. Pipet 2 mL of the sample solution, and add a mixture of
(2) Determine the infrared absorption spectrum of Ne-
chloroform and ethanol (99.5) (1:1) to make exactly 100 mL.
ostigmine Methylsulfate, previously dried, as directed in the
Pipet 5 mL of this solution, add a mixture of chloroform and
potassium bromide disk method under Infrared Spec-
ethanol (99.5) (1:1) to make exactly 50 mL, and use this solu-
trophotometry <2.25>, and compare the spectrum with the
tion as the standard solution. Perform the test with these so-
Reference Spectrum or the spectrum of dried Neostigmine
lutions as directed under Thin-layer Chromatography <2.03>.
Methylsulfate Reference Standard: both spectra exhibit simi-
Spot 10 mL each of the sample solution and standard solution
lar intensities of absorption at the same wave numbers.
on a plate of silica gel with ‰uorescent indicator for thin-layer
chromatography. Develop the plate with a mixture of pH <2.54> Dissolve 1.0 g of Neostigmine Methylsulfate in
hexane, dichloromethane, tetrahydrofuran and acetic acid 10 mL of freshly boiled and cooled water: the pH of the solu-
(100) (50:30:17:3) to a distance of about 12 cm, and air-dry tion is between 3.0 and 5.0.
the plate. Examine under ultraviolet light (main wavelength:
Melting point <2.60> 145 – 1499
C
254 nm): the spots other than the principal spot and the spot
of the starting point from the sample solution are not more Purity (1) Clarity and color of solution—Dissolve 1.0 g of
intense than the spot from the standard solution. Neostigmine Methylsulfate in 10 mL of water: the solution is
clear and colorless.
Loss on drying <2.41> Not more than 0.5z (1 g, 1059C,
(2) Sulfate—Dissolve 0.20 g of Neostigmine Methylsul-
3 hours).
fate in 10 mL of water, add 1 mL of dilute hydrochloric acid
Residue on ignition <2.44> Not more than 0.1z (1 g). and 1 mL of barium chloride TS: no turbidity is produced im-
mediately.
Assay Weigh accurately about 0.5g of Naproxen, previous-
(3) Dimethylaminophenol—Dissolve 0.10 g of Neostig-
ly dried, add 100 mL of diluted methanol (4 in 5), dissolve by
mine Methylsulfate in 5 mL of water, add 1 mL of sodium
gentle warming if necessary, and titrate <2.50> with 0.1 mol W
hydroxide TS, and while cooling with ice, add 1 mL of dia-
L sodium hydroxide VS (indicator: 3 drops of phenolphtha-
zobenzenesulfonic acid TS: no color develops.
lein TS). Perform a blank determination, and make any
necessary correction. Loss on drying <2.41> Not more than 1.0z (1 g, 1059
C,
3 hours).
Each mL of 0.1 mol W
L sodium hydroxide VS
＝ 23.03 mg of C14H14O3 Residue on ignition <2.44> Not more than 0.1z (1 g).
Containers and storage Containers—Well-closed contain- Assay Weigh accurately about 25 mg each of Neostigmine
ers. Methylsulfate and Neostigmine Methylsulfate Reference
Storage—Light-resistant. Standard, previously dried, dissolve each in the mobile phase
to make exactly 50 mL, and use these solutions as the sample
solution and the standard solution, respectively. Perform the
Neostigmine Methylsulfate test with exactly 10 mL each of the sample solution and stan-
dard solution as directed under Liquid Chromatography
ネオスチグミンメチル硫酸塩 <2.01> according to the following conditions, and determine
the peak areas, A T and A S, of neostigmine in each solution.
Amount (mg) of C13H22N2O6S
＝WS×(A T/A S)
WS: Amount (mg) of Neostigmine Methylsulfate Refer-
ence Standard
Operating conditions—
Detector: An ultraviolet absorption photometer
C13H22N2O6S: 334.39
(wavelength: 259 nm).
3-(Dimethylcarbamoyloxy)-N,N,N-
Column: A stainless steel column 4.6 mm in inside di-
trimethylanilinium methyl sulfate [51-60-5 ]
ameter and 15 cm in length, packed with octadecylsilanized
silica gel for liquid chromatography (5 mm in particle di-
Neostigmine Methylsulfate, when dried, contains
ameter).
not less than 98.0z and not more than 102.0z of
Column temperature: A constant temperature of about
C13H22N2O6S.
259C.
Description Neostigmine Methylsulfate occurs as a white, Mobile phase: Dissolve 3.12 g of sodium dihydrogen-