August 2012 RESTRICTED ZINC ACETATE Draft proposal for The International Pharmacopoeia (August 2012) Draft for discussion This document was provided by a quality control expert. Should you have any comments thereon, please send these to Dr Herbert Schmidt, Medicines Quality Assurance Programme, Quality Assurance and Safety: Medicines, World Health Organization, 1211 Geneva 27, Switzerland; fax: (+41 22) 791 4730 or e-mail: schmidth@who.int with a copy to gaspardm@who.int by 17 September 2012. In order to speed up the process for receiving draft monographs and for sending comments, please let us have your e-mail address (to bonnyw@who.int) and we will add it to our electronic mailing list. Please specify if you wish to receive monographs. World Health Organization 2012 All rights reserved. This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any form or by any means outside these individuals and organizations (including the organizations' concerned staff and member organizations) without the permission of the World Health Organization. The draft should not be displayed on any web site. Please send any request for permission to: Dr Sabine Kopp, Medicines Quality Assurance Programme, Quality Assurance and Safety: Medicines, Department of Essential Medicines and Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland. Fax: (41-22) 791 4730; e-mail: kopps@who.int. The designations employed and the presentation of the material in this draft do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft. However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This draft does not necessarily represent the decisions or the stated policy of the World Health Organization.
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 consultation on specifications for medicines and quality control laboratory issues 29-31 May 2012 Draft sent out for comments following discussion at consultation on specifications for medicines and quality control laboratory issues August 2012 Collation of comments received August-September 2012 Discussion at forty-seventh meeting of the WHO Expert Committee on Specifications for Pharmaceutical Preparations 9-12 October 2012 Further follow-up action as required
page 3 Zinci Acetas Zinc Acetate C 6 H 6 O 4 Zn,2H 2 O 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 C 6 H 6 O 4 Zn,2H 2 O. 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
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 C 4 H 6 O 4 Zn,2H 2 O. Reagents and test solutions to be added Cadmium R. Cd A commercially available reagent of suitable grade. Cadmium standard (1000 µg Cd/ml) TS.
page 5 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 KMnO 4 per litre. ***