Working document QAS/12.489
August 2012
RESTRICTED
ZINC ACETATE
Draft proposal for The International Pharmacopoeia
(August 2012)
Draft for discussion
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Working document QAS/12.489
page 2
SCHEDULE FOR THE ADOPTION PROCESS OF DOCUMENT QAS/12.489
Draft proposal for revision of a published monograph in
The International Pharmacopoeia
ZINC ACETATE
Date
Discussion of preliminary draft revision at 29-31 May 2012
consultation on specifications for medicines
and quality control laboratory issues
Draft sent out for comments following
August 2012
discussion at consultation on specifications
for medicines and quality control laboratory
issues
Collation of comments received
August-September 2012
Discussion at forty-seventh meeting of the 9-12 October 2012
WHO Expert Committee on Specifications
for Pharmaceutical Preparations
Further follow-up action as required
Working document QAS/12.489
page 3
Zinci Acetas
Zinc Acetate
C6H6O4Zn,2H2O
Relative molecular mass. 219.5.
Chemical name. Zinc acetate dihydrate; CAS Reg. No. 5970-45-6.
Description. A white or almost white crystalline powder or flakes.
Solubility. Freely soluble in water; soluble in ethanol (~750 g/l) TS.
Category. Adjunct to oral rehydration salts in (prevention and) treatment of dehydration due
to diarrhoea; astringent.
Storage. Zinc acetate should be kept in a well-closed, non-metallic container.
Labelling. The designation on the container should state that the substance is in the
dihydrate form and indicate the quantity in terms of the equivalent amount of elemental zinc.
Requirements
Definition. Zinc acetate dihydrate contains not less than 99.0% and not more than 101.0% of
C6H6O4Zn,2H2O.
Identity tests
A. Dissolve 0.1 g in 5 ml of water R and add 0.2 ml of sodium hydroxide
(~400 g/l) TS. A white precipitate is formed. Add a further 2 ml of sodium hydroxide
(~400 g/l) TS. The precipitate dissolves. Add 10 ml of ammonium chloride (~100 g/l)
TS. The solution remains clear. Add 0.1 ml of sodium sulfide TS. A flocculent white
precipitate is formed.
B. Dissolve 0.2 g in 4 ml of water R and add 4 ml of ferric chloride (~65 g/l) TS. A redbrown colour is formed. Boil the solution; a red-brown precipitate is produced. Add
drop wise sufficient hydrochloric acid (~250 g/l) TS to dissolve the precipitate; a
yellow colour appears.
Clarity and colour of solution. A solution of 1 g in 10 ml of water R is clear and colourless.
pH value (1.13). pH of a 0.05 g/ml solution in carbon-dioxide-free water R, 5.8–7.0.
Aluminum. Determine by atomic absorption spectrophotometry 1.8 Atomic spectrometry:
emission and absorption, Method 1, at a wavelength of 309.3 nm using an aluminum hollow
cathode lamp, an acetylene-nitrous oxide flame, and a slit width of 0.5 nm. Dissolve 2.5 g in
Working document QAS/12.489
page 4
25 ml of cadmium-free and lead-free nitric acid (~200 g/l) TS. As a reference solution use
aluminum standard (10 µg Al/ml) TS; not more than 5 µg of Al per g.
Arsenic. Use a solution of 5.0 g in 50 ml of water R, add 10 ml of stannated hydrochloric
acid (~250 g/l) AsTS, and proceed as described under 2.2.5 Limit test for arsenic; not more
than 2 µg As per g.
Cadmium. Determine by atomic absorption spectrophotometry 1.8 Atomic spectrometry:
emission and absorption, Method 1, at a wavelength of 228.8 nm using a cadmium hollow
cathode lamp, an air-acetylene flame, and a slit width of 0.5 nm. Dissolve 2.5 g in 25 ml of
cadmium-free and lead-free nitric acid (~200 g/l) TS. As a reference solution use cadmium
standard (1000 µg Cd/ml) TS; not more than 2 µg of Cd per g.
Copper. Determine by atomic absorption spectrophotometry 1.8 Atomic spectrometry:
emission and absorption, Method 1, at a wavelength of 324.8 nm using a copper hollow
cathode lamp, an air-acetylene flame, and a slit width of 0.5 nm. Dissolve 1.25 g in 25 ml of
cadmium-free and lead-free nitric acid (~200 g/l) TS. As a reference solution use copper
standard (10 µg Cu/ml) TS; not more than 50 µg of Cu per g.
Chlorides. Dissolve 5.0 g in 25 ml of water R, and proceed as described under 2.2.1 Limit
test for chlorides; the chloride content is not more than 50 µg/g.
Iron. Determine by atomic absorption spectrophotometry 1.8 Atomic spectrometry: emission
and absorption, Method 1, at a wavelength of 248.3 nm using an iron hollow cathode lamp,
an air-acetylene flame, and a slit width of 0.2 nm. Dissolve 1.25 g in 25 ml of cadmium-free
and lead-free nitric acid (~200 g/l) TS. As a reference solution use iron standard (20 µg
Fe/ml) FeTS; not more than 50 µg of Fe per g.
Lead. Determine by atomic absorption spectrophotometry 1.8 Atomic spectrometry:
emission and absorption, Method 1, at a wavelength of 283.3 nm using a lead hollow cathode
lamp, an air-acetylene flame, and a slit width of 0.5 nm. Dissolve 5.0 g in 25 ml of cadmiumfree and lead-free nitric acid (~200 g/l) TS. As a reference solution use strong lead PbTS;
not more than 10 µg of Pb per g.
Reducing substances. Dissolve 1 g in 10 ml of water R. Boil with 90 ml of water R, add 5
ml of sulfuric acid (~100 g/l) TS and 1.5 ml of potassium permanganate (~0.3 g/l) TS; the
pink colour of the solution remains.
Sulfates. Dissolve 4.8 g in 25 ml of water R, and proceed as described under 2.2.2 Limit test
for sulfates; the sulfate content is not more than 100 µg/g.
Assay
Dissolve about 100 mg, accurately weighed, in 50 ml of acetic acid (~10 g/l) TS and proceed
with the titration as described under 2.5 Complexometric titrations for zinc. Each ml of
disodium edetate (0.05 mol/l) VS is equivalent to 10.98 mg of C4H6O4Zn,2H2O.
Reagents and test solutions to be added
Cadmium R.
Cd
A commercially available reagent of suitable grade.
Cadmium standard (1000 µg Cd/ml) TS.
Working document QAS/12.489
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Procedure. Dissolve 0.100 g of cadmium R in sufficient amount of equal volumes of
hydrochloric acid (~330 g/l) TS and water R and dilute to 100 ml with a 1% V/V solution of
hydrochloric acid (~330 g/l) TS.
Note. For the preparation of this test solution commercially available cadmium standard
solution 1000 µg Cd/ml can also be used.
Nitric acid (~1000 g/l), cadmium-free and lead-free, TS.
[nitric acid, cadmium-free and lead-free (70%.) R].
Nitric acid (~200 g/l), cadmium-free and lead-free, TS.
Procedure. Dilute 200 ml cadmium-free and lead-free nitric acid (~1000 g/l) TS with water
R to produce 1000 ml.
Potassium permanganate (~ 0.3 g/l) TS.
A solution of potassium permanganate R containing about 0.3 g of KMnO4 per litre.
***