Appendix XX A. Materials for Containers for Human Blood and Blood Components

(Ph. Eur. method 3.1.1)

NOTE: for materials based on plasticised poly(vinyl chloride) for containers for aqueous solutions for intravenous infusion, see text 3.1.14.

Plastic containers for the collection, storage, processing and administration of blood and its components may be manufactured from one or more polymers, if necessary with certain additives.

If all or part of the container consists of a material described in a text of the Pharmacopoeia, the quality of the material is controlled by the methods indicated in that text. (See 3.1.1.1. Materials based on plasticised poly(vinyl chloride) for containers for human blood and blood components).

In normal conditions of use the materials and containers made from such materials do not release monomers, or other substances, in amounts likely to be harmful nor do they lead to any abnormal modifications of the blood or blood components.

1. Materials Based on Plasticised Poly(Vinyl Chloride) for Containers for Human Blood and Blood Components

(Ph. Eur. method 3.1.1.1)

DEFINITION

Materials based on plasticised poly(vinyl chloride) contain not less than 55 per cent of poly(vinyl chloride) and contain various additives, in addition to the high-molecular-mass polymer obtained by polymerisation of vinyl chloride.

Materials based on plasticised poly(vinyl chloride) for containers for human blood and blood components are defined by the nature and the proportions of the substances used in their manufacture.

PRODUCTION

Materials based on plasticised poly(vinyl chloride) are produced by polymerisation methods that guarantee a residual vinyl chloride content of less than 1 ppm. The manufacturing process is validated to demonstrate that the product complies with the following test.

Vinyl chloride

Head-space gas chromatography (2.2.28).

Internal standard solution Using a microsyringe, inject 10 µL of ether R into 20.0 mL of dimethylacetamide R, immersing the tip of the needle in the solvent. Immediately before use, dilute the solution 1000-fold with dimethylacetamide R.

Test solution Place 1.000 g of the material to be examined in a 50 mL vial and add 10.0 mL of the internal standard solution. Close the vial and secure the stopper. Shake, avoiding contact between the stopper and the liquid. Place the vial in a water-bath at 60 ± 1 °C for 2 h.

Vinyl chloride primary solutionPrepare in a fume cupboard. Place 50.0 mL of dimethylacetamide R in a 50 mL vial, stopper the vial, secure the stopper and weigh to the nearest 0.1 mg. Fill a 50 mL polyethylene or polypropylene syringe with gaseous vinyl chloride R, allow the gas to remain in contact with the syringe for about 3 min, empty the syringe and fill again with 50 mL of gaseous vinyl chloride R. Fit a hypodermic needle to the syringe and reduce the volume of gas in the syringe from 50 mL to 25 mL. Inject the remaining 25 mL of vinyl chloride slowly into the vial shaking gently and avoiding contact between the liquid and the needle. Weigh the vial again; the increase in mass is about 60 mg (1 µL of the solution thus obtained contains about 1.2 µg of vinyl chloride). Allow to stand for 2 h. Keep the primary solution in a refrigerator.

Vinyl chloride standard solution Vinyl chloride primary solution, dimethylacetamide R (1:3 V/V).

Reference solutions Place 10.0 mL of the internal standard solution in each of six 50 mL vials. Close the vials and secure the stoppers. Inject 1 µL, 2 µL, 3 µL, 5 µL and 10 µL, respectively, of the vinyl chloride standard solution into five of the vials. The six solutions thus obtained contain, respectively, 0 µg, about 0.3 µg, 0.6 µg, 0.9 µg, 1.5 µg and 3 µg of vinyl chloride. Shake, avoiding contact between the stopper and the liquid. Place the vials in a water-bath at 60 ± 1 °C for 2 h.

Column:

— material: stainless steel;

— size: l = 3 m, Ø = 3 mm;

— stationary phase: silanised diatomaceous earth for gas chromatography R impregnated with 5 per cent m/m of dimethylstearamide R and 5 per cent m/m of macrogol 400 R.

Carrier gasnitrogen for chromatography R.

Flow rate 30 mL/min.

Temperature:

— column: 45 °C;

— injection port: 100 °C;

— detector: 150 °C.

Detection Flame ionisation.

Injection 1 mL of the headspace.

Limit:

— vinyl chloride: maximum 1 ppm.

Additives

Depending on the intended use of the polymers, they contain additives to optimise their processing or their chemical, physical and mechanical properties. These additives are chosen from the following list, which specifies for each substance the maximum allowable content:

— di(2-ethylhexyl)phthalate (plastic additive 01): maximum 40 per cent;

— zinc octanoate (zinc 2-ethylhexanoate) (plastic additive 02): maximum 1 per cent;

— calcium stearate or zinc stearate: maximum 1 per cent or 1 per cent of a mixture of the two;

— N,N′-diacylethylenediamines (plastic additive 03): maximum 1 per cent;

— one of the following epoxidised oils: maximum 10 per cent or 10 per cent of a mixture of the two:

— epoxidised soya oil (plastic additive 04), of which the oxiran oxygen content is 6 per cent to 8 per cent and the iodine value is not greater than 6;

— epoxidised linseed oil (plastic additive 05), of which the oxiran oxygen content is not greater than 10 per cent and the iodine value is not greater than 7.

The supplier of the material must be able to demonstrate that the qualitative and quantitative composition of the type sample is satisfactory for each production batch.

CHARACTERS

Almost colourless or pale yellow powder, beads, granules or, after transformation, translucent sheets of varying thickness, with a slight odour. On combustion it gives off dense, black smoke.

IDENTIFICATION

If necessary, before use, cut the samples of the material to be examined into pieces of maximum dimension on a side of not greater than 1 cm.

To 2.0 g of the material to be examined add 200 mL of peroxide-free ether R and heat under a reflux condenser for 8 h. Separate the residue (residue B) and the solution (solution A) by filtration.

Evaporate solution A to dryness under reduced pressure in a water-bath at 30 °C. Dissolve the residue in 10 mL of toluene R (solution A1). Dissolve residue B in 60 mL of ethylene chloride R, heating on a water-bath under a reflux condenser. Filter. Add the solution obtained dropwise and with vigorous shaking to 600 mL of heptane R heated almost to boiling. Separate the coagulum (coagulum B1) and the organic solution by hot filtration. Allow the latter to cool; separate the precipitate that forms (precipitate B2) and filter through a tared sintered-glass filter (40) (2.1.2).

A. Infrared absorption spectrophotometry (2.2.24).

Preparation Dissolve coagulum B1 in 30 mL of tetrahydrofuran R and add, in small volumes with shaking, 40 mL of anhydrous ethanol R. Separate the precipitate (precipitate B3) by filtration and dry in vacuo at a temperature not exceeding 50 °C over diphosphorus pentoxide R. Dissolve a few milligrams of precipitate B3 in 1 mL of tetrahydrofuran R, place a few drops of the solution obtained on a sodium chloride plate and evaporate to dryness in an oven at 100-105 °C.

Comparisonpoly(vinyl chloride) CRS.

B. Infrared absorption spectrophotometry (2.2.24).

Examine residue C obtained in the test for plastic additives 01, 04 and 05.

Comparisonplastic additive 01 CRS.

TESTS

If necessary, before use, cut the samples of the material to be examined into pieces of maximum dimension on a side of not greater than 1 cm.

Solution S1

Place 5.0 g of the material to be examined in a combustion flask. Add 30 mL of sulfuric acid R and heat until a black, syrupy mass is obtained. Cool and add carefully 10 mL of strong hydrogen peroxide solution R. Heat gently. Allow to cool and add 1 mL of strong hydrogen peroxide solution R; repeat by alternating evaporation and addition of hydrogen peroxide solution until a colourless liquid is obtained. Reduce the volume to about 10 mL. Cool and dilute to 50.0 mL with water R.

Solution S2

Place 25 g of the material to be examined in a borosilicate-glass flask. Add 500 mL of water R and cover the neck of the flask with a borosilicate-glass beaker. Heat in an autoclave at 121 ± 2 °C for 20 min. Allow to cool, decant the solution and make up to 500 mL with water R.

Appearance of solution S2

Solution S2 is clear (2.2.1) and colourless (2.2.2, Method II).

Acidity or alkalinity

To 100 mL of solution S2 add 0.15 mL of BRP indicator solution R. Not more than 1.5 mL of 0.01 M sodium hydroxide is required to change the colour of the indicator to blue. To 100 mL of solution S2 add 0.2 mL of methyl orange solution R. Not more than 1.0 mL of 0.01 M hydrochloric acid is required to initiate the colour change of the indicator from yellow to orange.

Absorbance (2.2.25)

Evaporate 100.0 mL of solution S2 to dryness. Dissolve the residue in 5.0 mL of hexane R. From 250 nm to 310 nm the absorbance is not greater than 0.25.

Reducing substances

Carry out the test within 4 h of preparation of solution S2 To 20.0 mL of solution S2 add 1 mL of dilute sulfuric acid R and 20.0 mL of 0.002 M potassium permanganate. Boil under a reflux condenser for 3 min and cool immediately. Add 1 g of potassium iodide R and titrate immediately with 0.01 M sodium thiosulfate, using 0.25 mL of starch solution R as indicator. Carry out a blank titration using 20 mL of water R. The difference between the 2 titration volumes is not more than 2.0 mL.

Primary aromatic amines

Maximum 20 ppm.

To 2.5 mL of solution A1 obtained during the identification, add 6 mL of water R and 4 mL of 0.1 M hydrochloric acid. Shake vigorously and discard the upper layer. To the aqueous layer add 0.4 mL of a freshly prepared 10 g/L solution of sodium nitrite R. Mix and allow to stand for 1 min. Add 0.8 mL of a 25 g/L solution of ammonium sulfamate R, allow to stand for 1 min and add 2 mL of a 5 g/L solution of naphthylethylenediamine dihydrochloride R. After 30 min, any colour in the solution is not more intense than that in a standard prepared at the same time and in the same manner, replacing the aqueous layer with a mixture of 1 mL of a 0.01 g/L solution of naphthylamine R in 0.1 M hydrochloric acid, 5 mL of water R and 4 mL of 0.1 M hydrochloric acid.

Plastic additives 01, 04 and 05

Thin-layer chromatography (2.2.27).

Reference solutions Prepare 10 mg/mL solutions of plastic additive 01 CRS, plastic additive 04 CRS and plastic additive 05 CRS, respectively, in toluene R.

PlateTLC silica gel F₂₅₄ plate R.

Mobile phasetoluene R.

Application 0.5 mL of solution A1 obtained during the identification, as a band 30 mm by 3 mm, and 5 µL of each reference solution.

Development Over 2/3 of the plate.

Drying In air.

Detection A Examine in ultraviolet light at 254 nm.

Locate the zone corresponding to plastic additive 01 (R_F = about 0.4). Remove the area of silica gel corresponding to this zone and shake with 40 mL of ether R for 1 min. Filter, rinse with 2 quantities, each of 10 mL, of ether R, add the rinsings to the filtrate and evaporate to dryness. The residue (residue C) weighs not more than 40 mg.

Detection B Expose the plate to iodine vapour for 5 min.

Examine the chromatogram and locate the zone corresponding to plastic additives 04 and 05 (R_F = 0). Remove the area of silica gel corresponding to this zone. Similarly remove a corresponding area of silica gel as a blank reference. Separately shake both samples for 15 min with 40 mL of methanol R. Filter, rinse with 2 quantities, each of 10 mL, of methanol R, add the rinsings to the filtrate and evaporate to dryness. The difference between the masses of both residues is not more than 10 mg.

Plastic additive 03

Wash precipitate B2 obtained during the identification and contained in the tared sintered-glass filter (40) (2.1.2) with anhydrous ethanol R. Dry to constant mass over diphosphorus pentoxide R and weigh the filter. The residue weighs not more than 20 mg.

Infrared absorption spectrophotometry (2.2.24).

Preparation The residue obtained above. When the amount of residue is insufficient to prepare a disc, record the spectrum of the residue placed between 2 plates transparent to infrared radiation or examine by attenuated total reflectance (ATR).

Comparisonplastic additive 03 CRS.

Barium

Maximum 5 ppm.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Test solution Ignite 1.0 g of the material to be examined in a silica crucible. Take up the residue with 10 mL of hydrochloric acid R and evaporate to dryness on a water-bath. Take up the residue with 20 mL of 0.1 M hydrochloric acid.

Reference solution A solution containing 0.25 ppm of barium prepared by dilution of barium standard solution (50 ppm Ba) R with 0.1 M hydrochloric acid.

Wavelength Use the emission of barium at 455.40 nm, the spectral background being taken at 455.30 nm.

Verify the absence of barium in the hydrochloric acid used.

Cadmium

Maximum 0.6 ppm.

Atomic absorption spectrometry (2.2.23, Method I).

Test solution Evaporate 10 mL of solution S1 to dryness. Take up the residue using 5 mL of a 1 per cent V/V solution of hydrochloric acid R, filter and dilute the filtrate to 10.0 mL with the same acid solution.

Reference solutions Prepare the reference solutions using cadmium standard solution (0.1 per cent Cd) R, diluting with a 1 per cent V/V solution of hydrochloric acid R.

Source Cadmium hollow-cathode lamp.

Wavelength 228.8 nm.

Atomisation device Air-acetylene flame.

Verify the absence of cadmium in the hydrochloric acid used.

Calcium

Maximum 0.07 per cent.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Test solution Use the test solution prepared for the determination of barium.

Reference solution A solution containing 50.0 ppm of calcium prepared by dilution of calcium standard solution (400 ppm Ca) R with 0.1 M hydrochloric acid.

Wavelength Use the emission of calcium at 315.89 nm, the spectral background being taken at 315.60 nm.

Verify the absence of calcium in the hydrochloric acid used.

Tin

Maximum 20 ppm.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Test solution Dilute solution S1 10-fold with water R immediately before use.

Reference solution Introduce 2 mL of tin standard solution (5 ppm Sn) R into a 50 mL flask containing 5 mL of a 20 per cent V/V solution of sulfuric acid R and dilute to 50 mL with water R immediately before use.

Wavelength Use the emission of tin at 189.99 nm, the spectral background being taken at 190.10 nm.

Verify the absence of tin in the sulfuric acid used.

Zinc

Maximum 0.2 per cent.

Atomic absorption spectrometry (2.2.23, Method I).

Test solution Dilute solution S1 100-fold with 0.1 M hydrochloric acid.

Reference solutions Prepare the reference solutions using zinc standard solution (100 ppm Zn) R, diluting with 0.1 M hydrochloric acid.

Source Zinc hollow-cathode lamp.

Wavelength 213.9 nm.

Atomisation device Air-acetylene flame.

Verify the absence of zinc in the hydrochloric acid used.

Heavy metals (2.4.8)

Maximum 50 ppm.

To 10 mL of solution S1 add 0.5 mL of phenolphthalein solution R and then strong sodium hydroxide solution R until a pale pink colour is obtained. Dilute to 25 mL with water R. 12 mL of the solution complies with test A. Prepare the reference solution using lead standard solution (2 ppm Pb) R.

Water extractable substances

Maximum 0.3 per cent.

Evaporate 50 mL of solution S2 to dryness on a water-bath and dry in an oven at 100-105 °C to constant mass. Carry out a blank test with 50.0 mL of water R. The residue weighs not more than 7.5 mg taking into account the blank test.

ASSAY

Carry out the oxygen-flask method (2.5.10) using 50.0 mg of the material to be examined. Absorb the combustion products in 20 mL of 1 M sodium hydroxide. To the solution obtained add 2.5 mL of nitric acid R. Titrate with 0.1 M silver nitrate, determining the end-point potentiometrically (2.2.20). Carry out a blank titration.

1 mL of 0.1 M silver nitrate is equivalent to 6.25 mg of poly(vinyl chloride).

Additional tests for sterile plastic containers for human blood and blood components are described in chapter3.2. Containers and relevant sub-chapters.

An additional test for the absorbance of an anticoagulant solution is described in chapter 3.2.5. Sterile containers of plasticised poly(vinyl chloride) for human blood containing anticoagulant solution.

2. Materials Based on Plasticised Poly(Vinyl Chloride) for Tubing Used in Sets for the Transfusion of Blood and Blood Components

(Ph. Eur. method 3.1.1.2)

DEFINITION

Content

Minimum 55 per cent of poly(vinyl chloride).

The plasticiser used is di(2-ethylhexyl) phthalate (plastic additive 01).

PRODUCTION

Vinyl chloride

Head-space gas chromatography (2.2.28).

Vinyl chloride standard solution Vinyl chloride primary solution, dimethylacetamide R (1:3 V/V).

Reference solutions Place 10.0 mL of the internal standard solution in each of six 50 mL vials. Close the vials and secure the stoppers. Inject 1 µL, 2 µL, 3 µL, 5 µL and 10 µL, respectively, of the vinyl chloride standard solution into 5 of the vials. The 6 solutions thus obtained contain respectively, 0 µg, about 0.3 µg, 0.6 µg, 0.9 µg, 1.5 µg and 3 µg of vinyl chloride. Shake, avoiding contact between the stopper and the liquid. Place the vials in a water-bath at 60 ± 1 °C for 2 h.

Column:

— material: stainless steel;

— size: l = 3 m, Ø = 3 mm;

— stationary phase: silanised diatomaceous earth for gas chromatography R impregnated with 5 per cent m/m of dimethylstearamide R and 5 per cent m/m of macrogol 400 R.

Carrier gasnitrogen for chromatography R.

Flow rate 30 mL/min.

Temperature:

— column: 45 °C;

— injection port: 100 °C;

— detector: 150 °C.

Detection Flame ionisation.

Injection 1 mL of the head space.

Limit:

— vinyl chloride: maximum 1 ppm.

The supplier of the material must be able to demonstrate that the qualitative and quantitative composition of the type sample is satisfactory for each production batch.

CHARACTERS

Almost colourless or pale-yellow material in the form of powder, beads, granules or, after transformation, tubes with a slight odour. On combustion it gives off dense, black smoke.

IDENTIFICATION

If necessary, cut the samples of the material to be examined into pieces with a maximum dimension on a side of not greater than 1 cm.

A. To 0.5 g of the material to be examined add 30 mL of tetrahydrofuran R. Heat with stirring on a water-bath in a fume cupboard for 10 min. The material dissolves completely. Add methanol R dropwise with stirring. A granular precipitate is formed. Filter the precipitate and dry at 60 °C. Examine the precipitate by infrared absorption spectrophotometry (2.2.24). Dissolve 50 mg in 2 mL of tetrahydrofuran R and pour on a glass slide. Dry in an oven at 80 °C, remove the film and fix on a suitable mount. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with poly(vinyl chloride) CRS.

B. Infrared absorption spectrophotometry (2.2.24). Examine the residue obtained in the test for plastic additive 01.

Comparisonplastic additive 01 CRS.

TESTS

If necessary, cut the samples of the material to be examined into pieces with a maximum dimension on a side of not greater than 1 cm.

Solution S1

Solution S2

Place 25 g of the material to be examined in a borosilicate-glass flask. Add 500 mL of water R and cover the neck of the flask with a borosilicate-glass beaker. Heat in an autoclave at 121 ± 2 °C for 20 min. Allow to cool. Decant the solution and make up to 500 mL with water R.

Appearance of solution S2

Solution S2 is clear (2.2.1) and colourless (2.2.2, Method II).

Plastic additive 01

Thin-layer chromatography (2.2.27).

Test solution To 2.0 g of the material to be examined add 200 mL of peroxide-free ether R and heat under a reflux condenser for 8 h. Separate the residue and the solution by filtration and evaporate the solution to dryness under reduced pressure in a water-bath at 30 °C. Dissolve the residue in 10 mL of toluene R.

Reference solution Dissolve 0.8 g of plastic additive 01 CRS in toluene R and dilute to 10 mL with the same solvent.

PlateTLC silica gel F₂₅₄ plate R.

Mobile phasetoluene R.

Application 0.5 mL of the test solution and 5 µL of the reference solution, as a band 30 mm by 3 mm.

Development Over 2/3 of the plate.

Drying In air.

Detection In ultraviolet light at 254 nm.

Locate the zone corresponding to plastic additive 01. Remove the area of silica gel corresponding to this zone and shake with 40 mL of ether R. Filter without loss and evaporate to dryness. The residue weighs not more than 40 mg.

Barium

Maximum 5 ppm.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Reference solution A solution containing 0.25 ppm of barium prepared by dilution of barium standard solution (50 ppm Ba) R with 0.1 M hydrochloric acid.

Wavelength Use the emission of barium at 455.40 nm, the spectral background being taken at 455.30 nm.

Verify the absence of barium in the hydrochloric acid used.

Cadmium

Maximum 0.6 ppm.

Atomic absorption spectrometry (2.2.23, Method I).

Test solution Evaporate 10.0 mL of solution S1 to dryness. Take up the residue using 5 mL of a 1 per cent V/V solution of hydrochloric acid R, filter and dilute the filtrate to 10.0 mL with the same acid.

Reference solutions Prepare the reference solutions using cadmium standard solution (0.1 per cent Cd) R, diluting with a 1 per cent V/V solution of hydrochloric acid R.

Source Cadmium hollow-cathode lamp.

Wavelength 228.8 nm.

Atomisation device Air-acetylene flame.

Verify the absence of cadmium in the hydrochloric acid used.

Tin

Maximum 20 ppm.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Test solution Dilute solution S1 10-fold with water R immediately before use.

Wavelength Use the emission of tin at 189.99 nm, the spectral background being taken at 190.10 nm.

Verify the absence of tin in the sulfuric acid used.

Heavy metals (2.4.8)

Maximum 50 ppm.

ASSAY

To 0.500 g of the material to be examined add 30 mL of tetrahydrofuran R and heat with stirring on a water-bath in a fume cupboard for 10 min. The material dissolves completely. Add 60 mL of methanol R dropwise with stirring. A granular precipitate of poly(vinyl chloride) is formed. Allow to stand for a few minutes. Continue addition of methanol R until no further precipitation is observed. Transfer to a sintered-glass filter (40) (2.1.2), using 3 small quantities of methanol R to aid transfer and to wash the precipitate. Dry the filter and the precipitate to constant mass at 60 °C and weigh.

Additional tests for sterilised sets are described in chapter3.2.6. Sets for the transfusion of blood and blood components.

3. Materials Based on Non-plasticised Poly(Vinyl Chloride) for Containers for Non-injectable, Aqueous Solutions

(Ph. Eur. method 3.1.10)

DEFINITION

Materials based on non-plasticised poly(vinyl chloride) that comply with the following specifications are suitable for the manufacture of containers for non-injectable aqueous solutions. They may also be used for solid forms for oral administration and in some cases, subject to special studies on the compatibility of the container with its contents, these materials may be suitable for the preparation of containers for suppositories. They consist of 1 or more poly(vinyl chloride/vinyl acetate) or of a mixture of poly(vinyl chloride) and poly(vinyl acetate) or of poly(vinyl chloride).

The chlorine content expressed as poly(vinyl chloride) is not less than 80 per cent.

They may contain not more than 15 per cent of copolymers based on acrylic and/or methacrylic acids and/or their esters, and/or on styrene and/or butadiene.

PRODUCTION

Materials based on non-plasticised poly(vinyl chloride) are produced by polymerisation methods that guarantee a residual vinyl chloride content of less than 1 ppm. The manufacturing process is validated to demonstrate that the product complies with the following test.

Vinyl chloride

Head-space gas chromatography (2.2.28).

Vinyl chloride primary solutionPrepare in a fume cupboard. Place 50.0 mL of dimethylacetamide R in a 50 mL vial, stopper the vial, secure the stopper and weigh to the nearest 0.1 mg. Fill a 50 mL polyethylene or polypropylene syringe with gaseous vinyl chloride R, allow the gas to remain in contact with the syringe for about 3 min, empty the syringe and fill again with 50 mL of gaseous vinyl chloride R. Fit a hypodermic needle to the syringe and reduce the volume of gas in the syringe from 50 mL to 25 mL. Inject these 25 mL of vinyl chloride slowly into the vial, shaking gently and avoiding contact between the liquid and the needle. Weigh the vial again; the increase in mass is about 60 mg (1 µL of the solution thus obtained contains about 1.2 µg of vinyl chloride). Allow to stand for 2 h. Keep the primary solution in a refrigerator.

Vinyl chloride standard solution Vinyl chloride primary solution, dimethylacetamide R (1:3 V/V).

Reference solutions Place 10.0 mL of the internal standard solution in each of six 50 mL vials. Close the vials and secure the stoppers. Inject 1 µL, 2 µL, 3 µL, 5 µL and 10 µL, respectively, of the vinyl chloride standard solution into 5 of the vials. The 6 solutions thus obtained contain respectively, 0 µg, about 0.3 µg, 0.6 µg, 0.9 µg, 1.5 µg and 3 µg of vinyl chloride. Shake, avoiding contact between the stopper and the liquid. Place the vials in a water-bath at 60 ± 1 °C for 2 h.

Column:

— material: stainless steel;

— size: l = 3 m, Ø = 3 mm;

— stationary phase: silanised diatomaceous earth for gas chromatography R impregnated with 5 per cent m/m of dimethylstearamide R and 5 per cent m/m of macrogol 400 R.

Carrier gasnitrogen for chromatography R.

Flow rate 30 mL/min.

Temperature:

— column: 45 °C;

— injection port: 100 °C;

— detector: 150 °C.

Detection Flame ionisation.

Injection 1 mL of the head space.

Limit:

— vinyl chloride: maximum 1 ppm.

Additives

Depending on the intended use of the polymers, they may contain additives to optimise their processing or their chemical, physical and mechanical properties. These additives are chosen from the following list, which specifies for each substance the maximum allowable content:

— epoxidised soya oil of which the oxiran oxygen content is 6 per cent to 8 per cent and the iodine value is not greater than 6: maximum 8 per cent;

— calcium salt or zinc salts of aliphatic fatty acids with more than 7 carbon atoms: maximum 1.5 per cent or maximum 1.5 per cent of their mixture;

— liquid paraffin: maximum 1.5 per cent;

— waxes: maximum 1.5 per cent;

— hydrogenated oils or esters of aliphatic fatty acids: maximum 2 per cent;

— macrogol esters: maximum 1.5 per cent;

— sorbitol: maximum 1.5 per cent;

— 2,4-dinonylphenyl phosphite, or di(4-nonylphenyl) phosphite or tris(nonylphenyl) phosphite: maximum 1 per cent.

They may contain one of the following groups of stabilisers (where isooctyl is, for example, 2-ethylhexyl):

— tin as di(isooctyl) 2,2′-[(dioctylstannylene)bis(thio)]diacetate containing about 27 per cent of tri(isooctyl) 2,2′,2″-[(monooctylstannylidyne)tris(thio)]triacetate: maximum 0.25 per cent;

— tin as a mixture containing not more than 76 per cent of di(isooctyl) 2,2′-[(dimethylstannylene)bis(thio)]diacetate and not more than 85 per cent of tri(isooctyl) 2,2′,2″-[(monomethylstannylidyne)tris(thio)]triacetate: maximum 0.25 per cent;

— 1-phenyleicosane-1,3-dione (benzoylstearoylmethane) or 2-(4-dodecylphenyl)indole or didodecyl 1,4-dihydropyridine-2,6-dimethyl-3,5-dicarboxylate: maximum 1 per cent or 1 per cent of a mixture of 2 of these.

Colouring materials may be added, provided that the safety of the material is demonstrated to the satisfaction of the competent authority. The material may be opacified with titanium dioxide.

The supplier of the material must be able to demonstrate that the qualitative and quantitative composition of the type sample is satisfactory for each production batch.

CHARACTERS

Appearance

Powder, beads, granules, sheets of varying thicknesses or samples taken from finished objects.

Solubility

Practically insoluble in water, soluble in tetrahydrofuran, slightly soluble in methylene chloride, insoluble in anhydrous ethanol.

They burn with an orange-yellow flame edged with green, giving off thick black smoke.

IDENTIFICATION

Infrared absorption spectrophotometry (2.2.24).

Preparation Dissolve residue A (see Tests: solution S2) in 5 mL of tetrahydrofuran R. Apply a few drops of the solution to a sodium chloride plate and evaporate to dryness in an oven at 100-105 °C.

Absorption maxima (tolerance ± 5 cm^-¹): at 2910 cm^-¹, 1425 cm^-¹, 1330 cm^-¹, 1252 cm^-¹, 958 cm^-¹ and 690 cm^-¹.

The spectrum obtained is identical to that of the material selected for the type sample.

TESTS

If necessary, cut the samples of the material to be examined into pieces with a maximum dimension on a side of not greater than 1 cm.

Solution S1

Place 25 g of the material to be examined in a borosilicate-glass flask. Add 500 mL of water R and cover the neck of the flask with a borosilicate-glass beaker. Heat in an autoclave for 121 ± 2 °C for 20 min. Allow to cool, decant the solution and make up to 500 mL with water R.

Solution S2

Dissolve 5.0 g of the material to be examined in 80 mL of tetrahydrofuran R and dilute to 100 mL with the same solvent. Filter if necessary (the solution may remain opalescent). To 20 mL of the solution add, dropwise and with gentle shaking, 70 mL of ethanol (96 per cent) R. Cool in ice for 1 h. Filter or centrifuge (residue A). Wash residue A with ethanol (96 per cent) R, add the washings to the filtrate or the centrifugation liquid and dilute to 100 mL with ethanol (96 per cent) R.

Solution S3

Place 5 g of the material to be examined in a borosilicate-glass flask with a ground-glass neck. Add 100 mL of 0.1 M hydrochloric acid and boil under a reflux condenser for 1 h. Allow to cool and allow the solids to settle.

Appearance of solution S1

Solution S1 is not more opalescent than reference suspension II (2.2.1) and is colourless (2.2.2, Method II).

Absorbance of solution S1 (2.2.25)

Evaporate 100 mL of solution S1 to dryness. Dissolve the residue in 5 mL of hexane R. Filter if necessary through a filter previously rinsed with hexane R. At wavelengths from 250 nm to 310 nm, the absorbance of the filtrate is not greater than 0.25.

Absorbance of solution S2 (2.2.25)

Maximum 0.2 for tin-stabilised materials or 0.4 for other materials determined between wavelengths of 250 nm and 330 nm on solution S2.

Extractable barium

Maximum 2 ppm.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Test solution Solution S3.

Reference solution A solution containing 0.1 ppm of barium prepared by dilution of barium standard solution (50 ppm Ba) R with 0.1 M hydrochloric acid.

Wavelength Use the emission of barium at 455.40 nm, the spectral background being taken at 455.30 nm.

Verify the absence of barium in the hydrochloric acid used.

Examined at 455.40 nm, the emission of the test solution is not greater than that of the reference solution.

Extractable cadmium

Maximum 0.6 ppm.

Atomic absorption spectrometry (2.2.23, Method I).

Test solution Solution S3.

Reference solution A solution containing 0.03 ppm of cadmium prepared by diluting cadmium standard solution (0.1 per cent Cd) R with 0.1 M hydrochloric acid.

Verify the absence of cadmium in the hydrochloric acid used.

Examined at 228.8 nm, the absorbance of the test solution is not greater than that of the reference solution.

Tin-stabilised materials

Maximum 0.25 per cent of Sn.

Tin stock solution Dilute 81 mg of plastic additive 23 CRS to 100.0 mL with tetrahydrofuran R.

Tin standard solution Dilute 20 mL of the tin stock solution to 100.0 mL with ethanol (96 per cent) R.

To 0.10 mL of solution S2 in a test tube add 0.05 mL of 1 M hydrochloric acid, 0.5 mL of potassium iodide solution R and 5 mL of ethanol (96 per cent) R. Mix thoroughly and wait for 5 min. Add 9 mL of water R and 0.1 mL of a 5 g/L solution of sodium sulfite heptahydrate R and mix thoroughly. Add 1.5 mL of dithizone solution R freshly diluted 100-fold with methylene chloride R, shake for 15 s and allow to stand for 2 min. At the same time prepare a reference solution in the same manner using 0.1 mL of the tin standard solution.

Any violet colour in the lower layer obtained with solution S2 is not more intense than that obtained with the reference solution. The greenish-blue colour of dithizone solution turns pink in the presence of tin.

Non-tin stabilised materials

Maximum 25 ppm of Sn.

To 5 mL of solution S2 in a test tube add 0.05 mL of 1 M hydrochloric acid and 0.5 mL of potassium iodide solution R. Mix thoroughly and wait for 5 min. Add 9 mL of water R and 0.1 mL of a 5 g/L solution of sodium sulfite heptahydrate R and mix thoroughly. If the solution obtained is not colourless, add the sodium sulfite solution in 0.05 mL fractions. Add 1.5 mL of dithizone solution R freshly diluted 100-fold with methylene chloride R, shake for 15 s and allow to stand for 2 min. At the same time prepare a reference solution in the same manner using 0.05 mL of the tin standard solution (see test above).

Any violet colour in the lower layer obtained with solution S2 is not more intense than that obtained with the reference solution.

Extractable heavy metals (2.4.8)

Maximum 20 ppm.

12 mL of solution S3 complies with test A. Prepare the reference solution using 10 mL of lead standard solution (1 ppm Pb) R.

Extractable zinc

Maximum 100 ppm.

Atomic absorption spectrometry (2.2.23, Method I).

Test solution Solution S3 diluted 10-fold with water R.

Reference solution A solution containing 0.50 ppm of zinc prepared by dilution of zinc standard solution (5 mg/mL Zn) R with 0.01 M hydrochloric acid.

Verify the absence of zinc in the hydrochloric acid used.

Examined at 214.0 nm, the absorbance of the test solution is not greater than that of the reference solution.

Sulfated ash (2.4.14)

Maximum 1.0 per cent, determined on 1.0 g; maximum 4.0 per cent when the materials are opacified with titanium dioxide.

ASSAY

1 mL of 0.1 M silver nitrate is equivalent to 6.25 mg of poly(vinyl chloride).

4. Materials based on Non-Plasticised Poly(Vinyl Chloride) for Containers for Solid Dosage Forms for Oral Administration

(Ph. Eur. method 3.1.11)

DEFINITION

Materials based on non-plasticised poly(vinyl chloride) for containers for solid dosage forms for oral administration are suitable for the manufacture of sheets or containers, and consist of 1 or more poly(vinyl chloride/vinyl acetate) or of a mixture of poly(vinyl chloride) and poly(vinyl acetate) or of poly(vinyl chloride).

The chlorine content expressed as poly(vinyl chloride) is not less than 80 per cent.

They may contain not more than 15 per cent of copolymers based on acrylic and/or methacrylic acids and/or their esters, and/or on styrene and/or butadiene.

PRODUCTION

Vinyl chloride

Head-space gas chromatography (2.2.28).

Vinyl chloride primary solutionPrepare in a fume cupboard. Place 50.0 mL of dimethylacetamide R in a 50 mL vial, stopper the vial, secure the stopper and weigh to the nearest 0.1 mg. Fill a 50 mL polyethylene or polypropylene syringe with gaseous vinyl chloride R, allow the gas to remain in contact with the syringe for about 3 min, empty the syringe and fill again with 50 mL of gaseous vinyl chloride R. Fit a hypodermic needle to the syringe and reduce the volume of gas in the syringe from 50 mL to 25 mL. Inject the 25 mL of vinyl chloride slowly into the vial, shaking gently and avoiding contact between the liquid and the needle. Weigh the vial again; the increase in mass is about 60 mg (1 µL of the solution thus obtained contains about 1.2 µg of vinyl chloride). Allow to stand for 2 h. Keep the primary solution in a refrigerator.

Vinyl chloride standard solution Vinyl chloride primary solution, dimethylacetamide R (1:3 V/V).

Reference solutions Place 10.0 mL of the internal standard solution in each of six 50 mL vials. Close the vials and secure the stoppers. Inject 1 µL, 2 µL, 3 µL, 5 µL and 10 µL, respectively, of the vinyl chloride standard solution into 5 of the vials. The 6 solutions thus obtained contain respectively, 0 µg, about 0.3 µg, 0.6 µg, 0.9 µg, 1.5 µg and 3 µg of vinyl chloride. Shake, avoiding contact between the stopper and the liquid. Place the vials in a water-bath at 60 ± 1 °C for 2 h.

Column:

— material: stainless steel;

— size: l = 3 m, Ø = 3 mm;

— stationary phase: silanised diatomaceous earth for gas chromatography R impregnated with 5 per cent m/m of dimethylstearamide R and 5 per cent m/m of macrogol 400 R.

Carrier gasnitrogen for chromatography R.

Flow rate 30 mL/min.

Temperature:

— column: 45 °C;

— injection port: 100 °C;

— detector: 150 °C.

Detection Flame ionisation.

Injection 1 mL of the head space.

Limit:

— vinyl chloride: maximum 1 ppm.

Additives

— epoxidised soya oil of which the oxiran oxygen content is 6 per cent to 8 per cent and the iodine value is not greater than 6 for tin-stabilised materials: maximum 2 per cent;

— epoxidised soya oil of which the oxiran oxygen content is 6 per cent to 8 per cent and the iodine value is not greater than 6 for non-tin-stabilised materials: maximum 3 per cent;

— calcium, magnesium or zinc salts of aliphatic fatty acids with more than 7 carbon atoms: maximum 1.5 per cent or maximum 1.5 per cent of their mixture;

— waxes: maximum 4 per cent;

— liquid paraffin: maximum 1.5 per cent;

— hydrogenated oils or esters of aliphatic fatty acids: maximum 2 per cent;

— the percentage sum of the 3 lubricants above: maximum 4 per cent;

— macrogol esters: maximum 1.5 per cent;

— sorbitol: maximum 1.5 per cent;

— 2,4-dinonylphenyl phosphite, or di(4-nonylphenyl) phosphite or tris(nonylphenyl) phosphite: maximum 1 per cent;

— calcium carbonate: maximum 1 per cent;

— silica: maximum 1 per cent.

They may contain one of the following groups of stabilisers (where isooctyl is, for example, 2-ethylhexyl):

— tin as di(isooctyl) 2,2′-[(dioctylstannylene)bis(thio)]diacetate containing about 27 per cent of tri(isooctyl) 2,2′2″-[(monooctylstannylidyne)tris(thio)]triacetate: maximum 0.25 per cent;

— tin as tri(isooctyl) 2,2′2″-[(monooctylstannylidyne)tris(thio)]triacetate: maximum 0.25 per cent;

— 1-phenyleicosane-1,3-dione (benzoylstearoylmethane): maximum 1 per cent.

Colouring materials may be added, provided that the safety of the material is demonstrated to the satisfaction of the competent authority. The material may be opacified with titanium dioxide.

The supplier of the material must be able to demonstrate that the qualitative and quantitative composition of the type sample is satisfactory for each production batch.

CHARACTERS

Appearance

Powder, beads, granules, sheets of varying thicknesses or samples taken from finished objects.

Solubility

Practically insoluble in water, soluble in tetrahydrofuran, slightly soluble in methylene chloride, practically insoluble in anhydrous ethanol.

They burn with an orange-yellow flame edged with green, giving off thick black smoke.

IDENTIFICATION

Infrared absorption spectrophotometry (2.2.24).

Absorption maxima (tolerance ± 5 cm^-¹): at 2910 cm^-¹, 1425 cm^-¹, 1330 cm^-¹, 1252 cm^-¹, 958 cm^-¹ and 690 cm^-¹.

The spectrum obtained is identical to that of the material selected for the type sample.

TESTS

If necessary, cut the samples of the material to be examined into pieces with a maximum dimension on a side of not greater than 1 cm.

Solution S1

Place 25 g of the material to be examined in a borosilicate-glass flask. Add 500 mL of water R and cover the neck of the flask with a borosilicate glass beaker. Heat in an autoclave for 121 ± 2 °C for 20 min. Allow to cool, decant the solution and make up to 500 mL with water R.

Solution S2

Solution S3

Appearance of solution S1

Solution S1 is not more opalescent than reference suspension II (2.2.1) and is colourless (2.2.2, Method II).

Absorbance of solution S1 (2.2.25)

Absorbance of solution S2 (2.2.25)

Maximum 1.0, determined between wavelengths of 250 nm and 330 nm on solution S2 for material that does not contain 1-phenyleicosane-1,3-dione; maximum 0.4, determined between wavelengths of 250 nm and 330 nm on a 10-fold dilution of solution S2 in ethanol (96 per cent) R for material that contains 1-phenyleicosane-1,3-dione.

Tin-stabilised materials

Maximum 0.25 per cent of Sn.

Tin stock solution Dilute 81 mg of plastic additive 23 CRS to 100.0 mL with tetrahydrofuran R.

Tin standard solution Dilute 20 mL of the tin stock solution to 100.0 mL with ethanol (96 per cent) R.

To 0.10 mL of solution S2 in a test-tube add 0.05 mL of 1 M hydrochloric acid, 0.5 mL of potassium iodide solution R and 5 mL of ethanol (96 per cent) R. Mix thoroughly and wait for 5 min. Add 9 mL of water R and 0.1 mL of a 5 g/L solution of sodium sulfite heptahydrate R and mix thoroughly. Add 1.5 mL of dithizone solution R freshly diluted 100-fold with methylene chloride R, shake for 15 s and allow to stand for 2 min. At the same time prepare a reference solution in the same manner using 0.1 mL of the tin standard solution.

Non-tin-stabilised materials

Maximum 25 ppm of Sn.

To 5 mL of solution S2 in a test-tube add 0.05 mL of 1 M hydrochloric acid and 0.5 mL of potassium iodide solution R. Mix thoroughly and wait for 5 min. Add 9 mL of water R and 0.1 mL of a 5 g/L solution of sodium sulfite heptahydrate R and mix thoroughly. If the solution obtained is not colourless, add the sodium sulfite solution in 0.05 mL fractions. Add 1.5 mL of dithizone solution R freshly diluted 100-fold with methylene chloride R, shake for 15 s and allow to stand for 2 min. At the same time prepare a reference solution in the same manner using 0.05 mL of the tin standard solution (see test above).

Any violet colour in the lower layer obtained with solution S2 is not more intense than that obtained with the reference solution.

Extractable heavy metals (2.4.8)

Maximum 20 ppm.

12 mL of solution S3 complies with test A. Prepare the reference solution using 10 mL of lead standard solution (1 ppm Pb) R.

Extractable zinc

Maximum 100 ppm.

Atomic absorption spectrometry (2.2.23, Method I).

Test solution Solution S3 diluted 10-fold with water R.

Reference solution A solution containing 0.50 ppm of zinc prepared by dilution of zinc standard solution (5 mg/mL Zn) R with 0.01 M hydrochloric acid.

Verify the absence of zinc in the hydrochloric acid used.

Examined at 214.0 nm, the absorbance of the test solution is not greater than that of the reference solution.

Sulfated ash (2.4.14)

Maximum 1.0 per cent, determined on 1.0 g; maximum 4.0 per cent when the materials are opacified with titanium dioxide.

ASSAY

1 mL of 0.1 M silver nitrate is equivalent to 6.25 mg of poly(vinyl chloride).

5. Materials Based on Plasticised Poly(Vinyl Chloride) for Containers for Aqueous Solutions for Intravenous Infusion

(Ph. Eur. method 3.1.14)

DEFINITION

Materials based on plasticised poly(vinyl chloride) for containers for aqueous solutions for intravenous infusion are defined by the nature and the proportions of the substances used in their manufacture.

PRODUCTION

Materials based on plasticised poly(vinyl chloride) are produced by polymerisation methods which guarantee a residual vinyl chloride content of less than 1 ppm. The production method used is validated in order to demonstrate that the product complies with the following test.

Vinyl chloride

Head space gas chromatography (2.2.28).

Vinyl chloride standard solution Vinyl chloride primary solution, dimethylacetamide R (1:3 V/V).

Reference solutions Place 10.0 mL of the internal standard solution in each of six 50 mL vials. Close the vials and secure the stoppers. Inject 1 µL, 2 µL, 3 µL, 5 µL and 10 µL, respectively, of the vinyl chloride standard solution into 5 of the vials. The 6 solutions thus obtained contain, respectively, 0 µg, about 0.3 µg, 0.6 µg, 0.9 µg, 1.5 µg and 3 µg of vinyl chloride. Shake, avoiding contact between the stopper and the liquid. Place the vials in a water-bath at 60 ± 1 °C for 2 h.

Column:

— material: stainless steel;

— size: l = 3 m, Ø = 3 mm;

— stationary phase: silanised diatomaceous earth for gas chromatography R impregnated with 5 per cent m/m of dimethylstearamide R and 5 per cent m/m of macrogol 400 R.

Carrier gasnitrogen for chromatography R.

Flow rate 30 mL/min.

Temperature:

— column: 45 °C;

— injection port: 100 °C;

— detector: 150 °C.

Detection Flame ionisation.

Injection 1 mL of the head-space.

Limit:

— vinyl chloride: maximum 1 ppm.

Additives

— di(2-ethylhexyl)phthalate (plastic additive 01): maximum 40 per cent;

— zinc octanoate (zinc 2-ethylhexanoate) (plastic additive 02): maximum 1 per cent;

— calcium stearate or zinc stearate: maximum 1 per cent or 1 per cent of a mixture of the two;

— N,N′-diacylethylenediamines (plastic additive 03): maximum 1 per cent;

— maximum 10 per cent of one of the following epoxidised oils or 10 per cent of a mixture of the two:

— epoxidised soya oil (plastic additive 04) of which the oxiran oxygen content is 6 per cent to 8 per cent and the iodine value is not greater than 6;

— epoxidised linseed oil (plastic additive 05) of which the oxiran oxygen content is not greater than 10 per cent and the iodine value is not greater than 7.

When colouring materials are added, ultramarine blue (plastic additive 06) is used. Other colouring materials may be added, provided that the safety of the material is demonstrated to the satisfaction of the competent authority.

The supplier of the material must be able to demonstrate that the qualitative and quantitative composition of the type sample is satisfactory for each production batch.

CHARACTERS

Colourless, slightly blue or pale yellow powder, beads, granules or, after transformation, translucent sheets of varying thickness, with a slight odour. On combustion it gives off dense, black smoke.

IDENTIFICATION

If necessary, before use, cut the samples of the material to be examined into pieces of maximum dimension on a side of not greater than 1 cm.

To 2.0 g of the material to be examined add 200 mL of peroxide-free ether R and heat under a reflux condenser for 8 h. Separate the residue (residue B) and the solution (solution A) by filtration.

Evaporate solution A to dryness under reduced pressure in a water-bath at 30 °C. Dissolve residue in 10 mL of toluene R (solution A1). Dissolve residue B in 60 mL of ethylene chloride R, heating on a water-bath under a reflux condenser. Filter. Add the obtained solution dropwise and with vigorous shaking to 600 mL of heptane R heated almost to boiling. Separate by hot filtration the coagulum (coagulum B1) and the organic solution. Allow the latter to cool; separate the precipitate that forms (precipitate B2) and filter through a tared sintered-glass filter (40) (2.1.2).

A. Infrared absorption spectrophotometry (2.2.24).

Comparisonpoly(vinyl chloride) CRS

B. Infrared absorption spectrophotometry (2.2.24).

Examine residue C obtained in the test for plastic additives 01, 04 and 05.

Comparisonplastic additive 01 CRS.

TESTS

If necessary, before use, cut the samples of the material to be examined into pieces of maximum dimension on a side of not greater than 1 cm.

Solution S1

Place 5.0 g of the material to be examined in a combustion flask. Add 30 mL of sulfuric acid R and heat until a black, syrupy mass is obtained. Cool and add carefully 10 mL of strong hydrogen peroxide solution R. Heat gently. Allow to cool and add 1 mL of strong hydrogen peroxide solution R; repeat by alternating evaporation and addition of strong hydrogen peroxide solution until a colourless liquid is obtained. Reduce the volume to about 10 mL. Cool and dilute to 50.0 mL with water R.

Solution S2

Appearance of solution S2

Solution S2 is clear (2.2.1) and colourless (2.2.2, Method II).

Acidity or alkalinity

Absorbance (2.2.25)

Evaporate 100.0 mL of solution S2 to dryness. Dissolve the residue in 5.0 mL of hexane R. From 250 nm to 310 nm the absorbance is not greater than 0.25.

Reducing substances

Carry out the test within 4 h of preparation of solution S2. To 20.0 mL of solution S2 add 1 mL of dilute sulfuric acid R and 20.0 mL of 0.002 M potassium permanganate. Boil under a reflux condenser for 3 min and cool immediately. Add 1 g of potassium iodide R and titrate immediately with 0.01 M sodium thiosulfate, using 0.25 mL of starch solution R as indicator. Carry out a blank titration using 20 mL of water R. The difference between the 2 titration volumes is not greater than 2.0 mL.

Primary aromatic amines

Maximum 20 ppm.

Plastic additives 01, 04 and 05

Thin-layer chromatography (2.2.27).

Reference solutions Prepare 10 mg/mL solutions of plastic additive 01 CRS, plastic additive 04 CRS and plastic additive 05 CRS, respectively, in toluene R.

PlateTLC silica gel F₂₅₄ plate R.

Mobile phasetoluene R.

Application 0.5 mL of solution A1 obtained during the identification, as a band 30 mm by 3 mm, and 5 µL of each reference solution.

Development Over 2/3 of the plate.

Drying In air.

Detection A Examine in ultraviolet light at 254 nm.

Detection B Expose the plate to iodine vapour for 5 min.

Plastic additive 03

Infrared absorption spectrophotometry (2.2.24).

Comparisonplastic additive 03 CRS.

Barium

Maximum 5 ppm.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Reference solution A solution containing 0.25 ppm of barium prepared by dilution of barium standard solution (50 ppm Ba) R with 0.1 M hydrochloric acid.

Wavelength Use the emission of barium at 455.40 nm, the spectral background being taken at 455.30 nm.

Verify the absence of barium in the hydrochloric acid used.

Cadmium

Maximum 0.6 ppm.

Atomic absorption spectrometry (2.2.23, Method I).

Reference solutions Prepare the reference solutions using cadmium standard solution (0.1 per cent Cd) R, diluting with a 1 per cent V/V solution of hydrochloric acid R.

Source Cadmium hollow-cathode lamp.

Wavelength 228.8 nm.

Atomisation device Air-acetylene flame.

Verify the absence of cadmium in the hydrochloric acid used.

Calcium

Maximum 0.07 per cent.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Test solution Use the test solution prepared for the determination of barium.

Reference solution A solution containing 50.0 ppm of calcium prepared by dilution of calcium standard solution (400 ppm Ca) R with 0.1 M hydrochloric acid.

Wavelength Use the emission of calcium at 315.89 nm, the spectral background being taken at 315.60 nm.

Verify the absence of calcium in the hydrochloric acid used.

Tin

Maximum 20 ppm.

Inductively coupled plasma-atomic emission spectrometry (2.2.57).

Test solution Dilute solution S1 10-fold with water R immediately before use.

Wavelength Use the emission of tin at 189.99 nm, the spectral background being taken at 190.10 nm.

Verify the absence of tin in the hydrochloric acid used.

Zinc

Maximum 0.2 per cent.

Atomic absorption spectrometry (2.2.23, Method I).

Test solution Dilute solution S1 100-fold with 0.1 M hydrochloric acid.

Reference solutions Prepare the reference solutions using zinc standard solution (100 ppm Zn) R, diluting with 0.1 M hydrochloric acid.

Source Zinc hollow-cathode lamp.

Wavelength 213.9 nm.

Atomisation device Air-acetylene flame.

Verify the absence of zinc in the hydrochloric acid used.

Heavy metals (2.4.8)

Maximum 50 ppm.

Water extractable substances

Maximum 0.3 per cent.

Evaporate 50.0 mL of solution S2 to dryness on a water-bath and dry in an oven at 100-105 °C to constant mass. Carry out a blank test with 50.0 mL of water R. The residue weighs not more than 7.5 mg taking into account the blank test.

ASSAY

1 mL of 0.1 M silver nitrate is equivalent to 6.25 mg of poly(vinyl chloride).