USP 36
Packaging and storage—Preserve in tight containers,
preferably at a temperature not exceeding 30°.
Labeling—Label it to indicate whether it is the decahydrate
or is anhydrous.
Identification—A solution (1 in 20) responds to the tests
for Sodium 〈191〉 and for Sulfate 〈191〉.
Acidity or alkalinity—To 10 mL of a solution, containing
the equivalent of 1.0 g of Na2SO4 · 10H2O in 20 mL of
water, add 1 drop of bromothymol blue TS: not more than
0.50 mL of either 0.010 N hydrochloric acid or 0.010 N
sodium hydroxide is required to change the color of the
solution.
Loss on drying 〈731〉—Dry at 105° for 4 hours: the dec-
ahydrate loses between 51.0% and 57.0% of its weight,
and the anhydrous form loses not more than 0.5% of its
weight.
Chloride 〈221〉—A portion equivalent to 1.0 g of Na2SO4 ·
10H2O shows no more chloride than corresponds to
0.30 mL of 0.020 N hydrochloric acid (0.02%).
Heavy metals 〈231〉—Dissolve a portion containing the
equivalent of 2.0 g of Na2SO4 · 10H2O in 10 mL of water,
add 2 mL of 0.1 N hydrochloric acid, then add water to
make 25 mL: the limit is 0.001%.
Assay—Weigh accurately a portion of Sodium Sulfate,
equivalent to about 400 mg of anhydrous sodium sulfate,
dissolve in 200 mL of water, and add 1 mL of hydrochloric
acid. Heat to boiling, and gradually add, in small portions
and while constantly stirring, an excess of hot barium chlo-
ride TS (about 8 mL). Heat the mixture on a steam bath for
1 hour, collect the precipitate of barium sulfate on a reten-
tive, ashless filter paper, wash until free from chloride when
tested with silver nitrate TS, and place the filter into a suita-
ble tared crucible. Carefully burn away the paper, and ig-
nite at 800 ± 25° to constant weight. The weight of the bar-
ium sulfate so obtained, multiplied by 0.6086, represents its
equivalent of Na2SO4.
Sodium Sulfate Injection
.
» Sodium Sulfate Injection is a sterile, concen-
trated solution of Sodium Sulfate in Water for In-
jection, which upon dilution is suitable for paren-
teral use. It contains not less than 95.0 percent
and not more than 105.0 percent of the labeled
amount of Na2SO4 · 10H2O.
Packaging and storage—Preserve in single-dose contain-
ers, preferably of Type I glass.
Labeling—Label it to indicate that it is to be diluted before
injection to render it isotonic (3.89% of Na2SO4 · 10H2O).
Identification—It responds to the tests for Sodium 〈191〉
and for Sulfate 〈191〉.
Pyrogen—When diluted with water for injection to contain
3.89% of Na2SO4 · 10H2O, it meets the requirements of the
Pyrogen Test 〈151〉.
pH 〈791〉: between 5.0 and 6.5.
Other requirements—It meets the requirements under In-
jections 〈1〉.
Assay—Transfer an accurately measured volume of Injec-
tion, equivalent to about 400 mg of sodium sulfate
(Na2SO4 · 10H2O), to a suitable vessel. Dilute if necessary, to
200 mL, and proceed as directed in the Assay under Sodium
Sulfate, beginning with “add 1 mL of hydrochloric acid.”
The weight of the barium sulfate so obtained, multiplied by
1.3804, represents its equivalent of Na2SO4 · 10H2O.
Official Monographs / Sodium 5177
Sodium Sulfide
.
Na2S · 9H2O 240.18
Sodium sulfide nonahydrate.
Disodium sulfide nonahydrate [1313-84-4].
» Sodium Sulfide contains not less than 98.0 per-
cent and not more than 103.0 percent of Na2S ·
9H2O.
Packaging and storage—Preserve in tight containers, and
store in a cool place.
Identification—[NOTE—Conduct this test in a fume hood.]
Transfer about 100 mg of Sodium Sulfide, to a suitable con-
tainer, add 10 mL of 3 N hydrochloric acid, and cover the
top of the container with filter paper saturated with a 0.2 M
lead acetate solution: a brownish or silvery-black color forms
on the paper.
Limit of iron—Dissolve about 5.0 g in 100 mL of water:
the solution is clear and colorless.
Limit of sulfite and thiosulfate—Dissolve 3.0 g in
200.0 mL of filtered and degassed water. Add 100.0 mL of
0.2 N zinc sulfate, mix, and allow to stand for 30 minutes.
Filter, add 1 mL of starch TS, and titrate 100.0 mL of the
filtrate with 0.01 N iodine VS: not more than 3.0 mL is re-
quired.
Assay—Transfer about 275 mg of Sodium Sulfide, accu-
rately weighed, to a 250-mL beaker, dissolve in 30 mL of
filtered and degassed water, and mix. Add 50.0 mL of 0.1 N
iodine while mixing, add 2 mL of hydrochloric acid, and al-
low to stand for 15 minutes in a dark place. Titrate with 0.1
N sodium thiosulfate VS to a pale yellow color. Add 5 mL of
starch TS, and titrate with 0.1 N sodium thiosulfate VS to a
clear endpoint. Perform a blank determination, and make
any necessary correction. Each mL of 0.1 N sodium thiosul-
fate is equivalent to 12.01 mg of Na2S · 9H2O.
Sodium Sulfide Topical Gel
.
» Sodium Sulfide Topical Gel contains not less
than 90.0 percent and not more than 120.0 per-
cent of the labeled amount of sodium sulfide
(Na2S · 9H2O) in a suitable gel base.
Packaging and storage—Preserve in tight containers at
controlled room temperature or in a cool place.
Identification—Proceed as directed for the Identification
test under Sodium Sulfide.
pH 〈791〉: between 11.5 and 13.5.
Assay—
Diluent—Transfer 500.0 mL of a 4.0 M sodium hydroxide
solution to a 1000-mL volumetric flask, and add about
67.0 g of edetate disodium and 36.0 g of ascorbic acid,
each accurately weighed. Dilute with water to volume, and
mix.
Assay preparation—Transfer an accurately weighed por-
tion of the Topical Gel, equivalent to about 30 mg of so-
dium sulfide, to a 100-mL volumetric flask, add 50 mL of
Diluent, and shake by mechanical means until the Topical
Gel is dispersed. Dilute with Diluent to volume, and mix.
Procedure—Transfer 30.0 mL of the Assay preparation to a
suitable beaker, and titrate with 0.01 M lead perchlorate VS,
determining the endpoint potentiometrically. Perform a
blank determination, and make any necessary correction.
Each mL of 0.01 M lead perchlorate is equivalent to
2.4018 mg of sodium sulfide (Na2S · 9H2O).
5178 Sodium / Official Monographs
Sodium Thiosulfate
.
Na2S2O3 · 5H2O 248.18
Na2S2O3 158.11
Thiosulfuric acid, disodium salt, pentahydrate;
Disodium thiosulfate pentahydrate [10102-17-7].
Anhydrous [7772-98-7].
DEFINITION
Sodium Thiosulfate contains NLT 99.0% and NMT 100.5%
of sodium thiosulfate (Na2S2O3), calculated on the anhy-
drous basis.
IDENTIFICATION
• A.
Sample solution: 100 mg/mL
Analysis: Add a few drops of iodine TS.
Acceptance criteria: The color is discharged.
• B. IDENTIFICATION TESTS—GENERAL, Sodium 〈191〉
Sample solution: 100 mg/mL
Acceptance criteria: Meets the requirements
• C. IDENTIFICATION TESTS—GENERAL, Thiosulfate 〈191〉
Sample solution: 100 mg/mL
Acceptance criteria: Meets the requirements
ASSAY
• PROCEDURE
Sample: 800 mg
Titrimetric system
(See Titrimetry 〈541〉.)
Mode: Direct titration
Titrant: 0.1 N iodine VS
Endpoint detection: Visual
Analysis: Dissolve the Sample in 30 mL of water. Adjust
with 3 N hydrochloric acid to a pH of 6.2–6.7, if neces-
sary. Titrate with Titrant, adding 3 mL of starch TS as
the endpoint is approached. Each mL of Titrant is equiv-
alent to 15.81 mg of sodium thiosulfate (Na2S2O3).
Acceptance criteria: 99.0%–100.5% on the anhydrous
basis
IMPURITIES
• CALCIUM
Sample solution: Dissolve 1 g in 20 mL of water.
Analysis: To the Sample solution add a few mL of ammo-
nium oxalate TS.
Acceptance criteria: No turbidity is produced.
• HEAVY METALS 〈231〉
Test preparation: Dissolve 1 g in 10 mL of water.
Analysis: To the Test preparation slowly add 5 mL of 3 N
hydrochloric acid, evaporate on a steam bath nearly to
dryness, and heat the residue at 150° for 1 h. Add
15 mL of water to the residue, boil gently for 2 min,
and filter. Heat the filtrate to boiling, and add sufficient
bromine TS to produce a clear solution and to provide
a slight excess of bromine. Boil the solution to expel
the excess bromine, cool to room temperature, add 1
drop of phenolphthalein TS, and neutralize with 1 N so-
dium hydroxide. Dilute with water to 25 mL.
Acceptance criteria: NMT 20 ppm
SPECIFIC TESTS
• WATER DETERMINATION 〈921〉
Sample: 1.0 g
Analysis: Dry the Sample under vacuum at 40°–45° for
16 h.
Acceptance criteria: 32.0%–37.0%
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers.
USP 36
Sodium Thiosulfate Injection
.
» Sodium Thiosulfate Injection is a sterile solution
of Sodium Thiosulfate in freshly boiled Water for
Injection. It contains not less than 95.0 percent
and not more than 105.0 percent of the labeled
amount of Na2S2O3 · 5H2O.
Packaging and storage—Preserve in single-dose contain-
ers, of Type I glass.
USP Reference standards 〈11〉—
USP Endotoxin RS
Identification—It responds to the Identification tests under
Sodium Thiosulfate.
Bacterial endotoxins 〈85〉—It contains not more than
0.03 USP Endotoxin Unit per mg of sodium thiosulfate.
pH 〈791〉: between 6.0 and 9.5.
Other requirements—It meets the requirements under In-
jections 〈1〉.
Assay—Transfer to a suitable container an accurately meas-
ured volume of Injection, containing about 1 g of sodium
thiosulfate, and adjust by the addition of 3 N hydrochloric
acid to a pH of between 6.2 and 6.7. Dilute with water to
about 20 mL, and titrate with 0.1 N iodine VS, adding 3 mL
of starch TS as the endpoint is approached. Each mL of
0.1 N iodine is equivalent to 24.82 mg of Na2S2O3 · 5H2O.
Somatropin
.
C990H1528N262O300S7 22,124.77 [12629-01-5].
» Somatropin is a protein hormone consisting of
191 amino acid residues, and its structure corre-
sponds to the major component of the growth
hormone extracted from human pituitary glands.
It is produced as a lyophilized powder or bulk
solution by methods based on recombinant DNA
technology. When prepared as a lyophilized
powder, it contains not less than 910 µg of so-
matropin per mg, calculated on the anhydrous
basis. When prepared as a bulk solution, it con-
tains not less than 910 µg of somatropin per mg
of total protein. The presence of host-cell DNA
and host-cell protein impurities in Somatropin is
process specific—the limits of these impurities are
determined by validated methods. Manufacturers
must demonstrate a correlation between the As-
say and a validated and approved growth-pro-
motion based bioassay. It may contain excipients.
[NOTE—One mg of anhydrous Somatropin is
equivalent to 3.0 USP Somatropin Units.]
Packaging and storage—Preserve in tight containers, and
store between –10° and –25°.
Labeling—The labeling states that the material is of recom-
binant DNA origin.