3.3.3. Plasticised PVC materials for tubing for transfusion of blood EUROPEAN PHARMACOPOEIA 10.

corresponding area of silica gel as a blank reference. Separately Atomisation device : air-acetylene flame.
shake both samples for 15 min with 40 mL of methanol R. Verify the absence of zinc in the hydrochloric acid used.
Filter, rinse with 2 quantities, each of 10 mL, of methanol R,
add the rinsings to the filtrate and evaporate to dryness. The Heavy metals (2.4.8): maximum 50 ppm.
difference between the masses of both residues is not more To 10 mL of solution S1 add 0.5 mL of phenolphthalein
than 10 mg. solution R and then strong sodium hydroxide solution R until
Barium : maximum 5 ppm. a pale pink colour is obtained. Dilute to 25 mL with water R.
12 mL of the solution complies with test A. Prepare the
Inductively coupled plasma-atomic emission spectrometry reference solution using lead standard solution (2 ppm Pb) R.
(2.2.57).
Water extractable substances : maximum 0.3 per cent.
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 Evaporate 50 mL of solution S2 to dryness on a water-bath
acid R and evaporate to dryness on a water-bath. Take up the and dry in an oven at 100-105 °C to constant mass. Carry out
residue with 20 mL of 0.1 M hydrochloric acid. 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.
Reference solution. A solution containing 0.25 ppm of
barium prepared by dilution of barium standard solution ASSAY
(50 ppm Ba) R with 0.1 M hydrochloric acid. Carry out the oxygen-flask method (2.5.10) using 50.0 mg of
Wavelength : use the emission of barium at 455.40 nm, the the material to be examined. Absorb the combustion products
spectral background being taken at 455.30 nm. in 20 mL of 1 M sodium hydroxide. To the solution obtained
Verify the absence of barium in the hydrochloric acid used. add 2.5 mL of nitric acid R. Titrate with 0.1 M silver nitrate,
determining the end-point potentiometrically (2.2.20). Carry
Cadmium : maximum 0.6 ppm.
out a blank titration.
Atomic absorption spectrometry (2.2.23, Method I).
1 mL of 0.1 M silver nitrate is equivalent to 6.25 mg of
Test solution. Evaporate 10 mL of solution S1 to dryness. poly(vinyl chloride).
Take up the residue using 5 mL of a 1 per cent V/V solution
Additional tests for sterile plastic containers for human blood
of hydrochloric acid R, filter and dilute the filtrate to 10.0 mL
and blood components are described in chapter 3.3. Containers
with the same acid solution.
for human blood and blood components, and materials used in
Reference solutions. Prepare the reference solutions using their manufacture ; transfusion sets and materials used in their
cadmium standard solution (0.1 per cent Cd) R, diluting with a manufacture ; syringes and relevant subsections.
1 per cent V/V solution of hydrochloric acid R.
An additional test for the absorbance of an anticoagulant
Source : cadmium hollow-cathode lamp. solution is described in general chapter 3.3.6. Sterile containers
Wavelength : 228.8 nm. of plasticised poly(vinyl chloride) for human blood containing
Atomisation device : air-acetylene flame. anticoagulant solution.
Verify the absence of cadmium in the hydrochloric acid used.
Calcium : maximum 0.07 per cent.
01/2020:30303
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 3.3.3. MATERIALS BASED ON
calcium prepared by dilution of calcium standard solution
(400 ppm Ca) R with 0.1 M hydrochloric acid. PLASTICISED POLY(VINYL
Wavelength : use the emission of calcium at 315.89 nm, the CHLORIDE) FOR TUBING USED
spectral background being taken at 315.60 nm. IN SETS FOR THE TRANSFUSION OF
Verify the absence of calcium in the hydrochloric acid used. BLOOD AND BLOOD COMPONENTS
Tin : maximum 20 ppm.
This general chapter is published for information.
Inductively coupled plasma-atomic emission spectrometry
(2.2.57). DEFINITION
Test solution. Dilute solution S1 10-fold with water R Materials based on plasticised poly(vinyl chloride) contain
immediately before use. not less than 55 per cent of poly(vinyl chloride) and contain
Reference solution. Introduce 2 mL of tin standard solution various additives, in addition to the high-molecular-mass
(5 ppm Sn) R into a 50 mL flask containing 5 mL of a 20 per polymer obtained by polymerisation of vinyl chloride.
cent V/V solution of sulfuric acid R and dilute to 50 mL with Materials based on plasticised poly(vinyl chloride) for
water R immediately before use. tubing used in sets for the transfusion of blood and blood
Wavelength : use the emission of tin at 189.99 nm, the spectral components are defined by the nature and the proportions of
background being taken at 190.10 nm. the substances used in their manufacture.
Verify the absence of tin in the sulfuric acid used. Connecting ports are also to be considered as tubing.
Zinc : maximum 0.2 per cent. PRODUCTION
Atomic absorption spectrometry (2.2.23, Method I). Materials based on plasticised poly(vinyl chloride) are
Test solution. Dilute solution S1 100-fold with 0.1 M produced by polymerisation methods that guarantee a residual
hydrochloric acid. vinyl chloride content of less than 1 ppm.
Reference solutions. Prepare the reference solutions using Vinyl chloride. Head-space gas chromatography (2.2.28).
zinc standard solution (100 ppm Zn) R, diluting with 0.1 M
hydrochloric acid. Internal standard solution. Using a microsyringe, inject 10 μL
of ether R into 20.0 mL of dimethylacetamide R, immersing
Source : zinc hollow-cathode lamp. the tip of the needle in the solvent. Immediately before use,
Wavelength : 213.9 nm. dilute the solution 1000-fold with dimethylacetamide R.

468 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.0 3.3.3. Plasticised PVC materials for tubing for transfusion of blood

Test solution. Place 1.000 g of the material to be examined in a Blood and blood components have different requirements, for
50 mL vial and add 10.0 mL of the internal standard solution. example with respect to gas exchange, storage temperature
Close the vial and secure the stopper. Shake, avoiding contact and the mechanical properties of the tubing. In addition, the
between the stopper and the liquid. Place the vial in a stability and the quality of blood or blood components during
water-bath at 60 ± 1 °C for 2 h. transfusion can be influenced by the plasticisers/additives
Vinyl chloride primary solution. Prepare in a fume cupboard. present in the materials used in the composition of the tubing.
Place 50.0 mL of dimethylacetamide R in a 50 mL vial, stopper To ensure the stability of blood and blood components during
the vial, secure the stopper and weigh to the nearest 0.1 mg. transfusion, the materials from which the tubing is composed
Fill a 50 mL polyethylene or polypropylene syringe with must be carefully selected according to the intended use.
gaseous vinyl chloride R, allow the gas to remain in contact
CHARACTERS
with the syringe for about 3 min, empty the syringe and fill
again with 50 mL of gaseous vinyl chloride R. Fit a hypodermic Almost colourless or pale-yellow material in the form of
needle to the syringe and reduce the volume of gas in the powder, beads, granules or, after transformation, tubes with a
syringe from 50 mL to 25 mL. Inject the remaining 25 mL of slight odour. On combustion it gives off dense, black smoke.
vinyl chloride slowly into the vial shaking gently and avoiding
contact between the liquid and the needle. Weigh the vial IDENTIFICATION
again ; the increase in mass is about 60 mg (1 μL of the solution If necessary, cut the samples of the material to be examined into
thus obtained contains about 1.2 μg of vinyl chloride). Allow pieces where the maximum size of a side is 1 cm.
to stand for 2 h. Keep the primary solution in a refrigerator. A. Infrared absorption spectrophotometry (2.2.24).
Vinyl chloride standard solution : vinyl chloride primary Preparation. To 0.5 g of the material to be examined
solution, dimethylacetamide R (1:3 V/V). add 30 mL of tetrahydrofuran R. Heat with stirring on a
Reference solutions. Place 10.0 mL of the internal standard water-bath in a fume cupboard for 10 min ; the material
solution in each of six 50 mL vials. Close the vials and dissolves completely. Add methanol R dropwise with
secure the stoppers. Inject 1 μL, 2 μL, 3 μL, 5 μL and 10 μL, stirring ; a granular precipitate is formed. Filter the
respectively, of the vinyl chloride standard solution into 5 of precipitate and dry at 60 °C. Examine the precipitate by
the vials. The 6 solutions thus obtained contain respectively, infrared absorption spectrophotometry (2.2.24). Dissolve
0 μg, about 0.3 μg, 0.6 μg, 0.9 μg, 1.5 μg and 3 μg of vinyl 50 mg in 2 mL of tetrahydrofuran R and pour on a glass
chloride. Shake, avoiding contact between the stopper and the slide. Dry in an oven at 80 °C, remove the film and fix
liquid. Place the vials in a water-bath at 60 ± 1 °C for 2 h. on a suitable mount. Examine by infrared absorption
Column : spectrophotometry (2.2.24).
– material : stainless steel ; Comparison : poly(vinyl chloride) CRS.
– size : l = 3 m, Ø = 3 mm ; B. Plastic additives 01, 24, 25, 26 and 27 (see Tests).
– stationary phase : silanised diatomaceous earth for gas TESTS
chromatography R impregnated with 5 per cent m/m of If necessary, cut the samples of the material to be examined into
dimethylstearamide R and 5 per cent m/m of macrogol pieces where the maximum size of a side is 1 cm.
400 R.
Solution S1. Place 5.0 g of the material to be examined in
Carrier gas : nitrogen for chromatography R.
a combustion flask. Add 30 mL of sulfuric acid R and heat
Flow rate : 30 mL/min. until a black, syrupy mass is obtained. Cool and add carefully
Temperature : 10 mL of strong hydrogen peroxide solution R. Heat gently.
– column : 45 °C ; Allow to cool and add 1 mL of strong hydrogen peroxide
solution R ; repeat by alternating evaporation and addition
– injection port : 100 °C ; of hydrogen peroxide solution until a colourless liquid is
– detector : 150 °C. obtained. Reduce the volume to about 10 mL. Cool and dilute
Detection : flame ionisation. to 50.0 mL with water R.
Injection : 1 mL. Solution S2. Place 25 g of the material to be examined in a
Limit : borosilicate-glass flask. Add 500 mL of water R and cover the
neck of the flask with a borosilicate-glass beaker. Heat in an
– vinyl chloride : maximum 1 ppm. autoclave at 121 ± 2 °C for 20 min. Allow to cool. Decant the
Additives solution and dilute to 500 mL with water R.
Depending on the intended use of the polymers, they contain Appearance of solution S2. Solution S2 is clear (2.2.1) and
additives to optimise their processing or their chemical, colourless (2.2.2, Method II).
physical and mechanical properties. Unless otherwise justified
Plastic additives 01, 24, 25, 26 and 27. Gas chromatography
and authorised, these additives are chosen from the following
(2.2.28) coupled with mass spectrometry (2.2.43).
list, which specifies for each substance the maximum
permitted content : Internal standard solution S3 : 1 mg/mL solution of di-n-octyl
phthalate R in tetrahydrofuran for chromatography R.
– di(2-ethylhexyl)phthalate (plastic additive 01): maximum
40 per cent ; Internal standard solution S4: 5 μg/mL solution of di-n-octyl
– cyclohexane 1,2-dicarboxylic acid, diisononyl ester (plastic phthalate R in anhydrous ethanol R.
additive 24): maximum 45 per cent ; Test solution. Cut 0.2 g of the material to be examined into
– butyryl tri-n-hexyl citrate (plastic additive 25) : maximum pieces about 0.5 cm in length. Dissolve the pieces in 12.5 mL of
45 per cent ; internal standard solution S3 using a polytetrafluoroethylene
magnetic stirring bar. Complete dissolution of the material to
– tris(2-ethylhexyl) trimellitate (plastic additive 26) : be examined is obtained after stirring for about 20-30 min.
maximum 45 per cent ; The poly(vinyl chloride) is precipitated as a white powder by
– bis(2-ethylhexyl) terephthalate (plastic additive 27): adding dropwise 37.5 mL of anhydrous ethanol R. Centrifuge,
maximum 45 per cent. then dilute 1.0 mL of the supernatant to 50.0 mL with
The supplier of the material must be able to demonstrate anhydrous ethanol R. The final concentration of the internal
that the qualitative and quantitative composition of the type standard in the test solution is 5 μg/mL.
sample is satisfactory for each production batch. The stock solutions may be stored at 4 °C for up to 2 weeks.

General Notices (1) apply to all monographs and other texts 469
3.3.3. Plasticised PVC materials for tubing for transfusion of blood EUROPEAN PHARMACOPOEIA 10.0

Stock solution (a). Dissolve 20.0 mg of plastic additive 01 CRS Substance Ion 1 [m/z] Ion 2 [m/z] Ion 3 [m/z]
in internal standard solution S4 and dilute to 20.0 mL with Plastic additive 01 149 167 279
internal standard solution S4.
Plastic additive 24 155 127 299
Stock solution (b). Dissolve 20.0 mg of plastic additive 24 CRS
in internal standard solution S4 and dilute to 20.0 mL with Plastic additive 25 71 213 315
internal standard solution S4.
Plastic additive 26 305 193 323
Stock solution (c). Dissolve 20.0 mg of plastic additive 25 CRS
in internal standard solution S4 and dilute to 20.0 mL with Plastic additive 27 261 149 167
internal standard solution S4. DnOP (internal standard) 149 279 167
Stock solution (d). Dissolve 20.0 mg of plastic additive 26 CRS
in internal standard solution S4 and dilute to 20.0 mL with Injection : 1 μL.
internal standard solution S4. Relative retention with reference to di-n-octyl
phthalate (retention time = about 22 min) : plastic
Stock solution (e). Dissolve 20.0 mg of plastic additive 27 CRS
additive 01 = about 0.80 ; plastic additive 24 = about 0.95-1,09 ;
in internal standard solution S4 and dilute to 20.0 mL with
plastic additive 27 = about 1.02 ; plastic additive
internal standard solution S4.
25 = about 1.14 ; plastic additive 26 = about 1.34.
Reference solutions (a1)-(a5). Dilute stock solution (a) with The specificity of the detection is checked by monitoring 3
internal standard solution S4 to obtain 5 reference solutions different ions for each substance using a mass spectrometer
containing 10-40 μg/mL of plastic additive 01 CRS. in SIM mode. Ion ratios are determined from the peak areas
Reference solutions (b1)-(b5). Dilute stock solution (b) with after the injection of a standard solution. The ratios in the
internal standard solution S4 to obtain 5 reference solutions table below are given for information.
containing 10-40 μg/mL of plastic additive 24 CRS. Substance Ion 1 Ion 2 Ion 3 Ion ratio Ion ratio
Reference solutions (c1)-(c5). Dilute stock solution (c) with [m/z] [m/z] [m/z] 2/1 3/1
internal standard solution S4 to obtain 5 reference solutions (%) (%)
containing 10-40 μg/mL of plastic additive 25 CRS. Plastic additive 01 149 167 279 50 30

Reference solutions (d1)-(d5). Dilute stock solution (d) with Plastic additive 24 155 127 299 30 13
internal standard solution S4 to obtain 5 reference solutions 45
Plastic additive 25 71 213 315 20
containing 10-40 μg/mL of plastic additive 26 CRS.
305 193 323 55 20
Reference solutions (e1)-(e5). Dilute stock solution (e) with Plastic additive 26
internal standard solution S4 to obtain 5 reference solutions Plastic additive 27 261 149 167 130 85
containing 10-40 μg/mL of plastic additive 27 CRS.
DnOP (internal 149 279 167 / /
Column : standard)
– material : fused silica ; System suitability :
– size : l = 30 m, Ø = 0.25 mm ; – resolution : if plastic additive 27 is tested, minimum 1.5
– stationary phase : phenyl(5)methyl(95)polysiloxane R (film between the peaks due to the internal standard and plastic
thickness 0.25 μm). additive 27 ;
– repeatability : maximum relative standard deviation of
Carrier gas : helium for chromatography R. 1.0 per cent for the retention time of the peak due to the
Flow rate : 1 mL/min. plastic additive, determined on 6 injections of a reference
Split ratio : 1:20. solution of each plastic additive tested situated in the
middle of the calibration range (e.g. 20 μg/mL); maximum
Temperature : relative standard deviation of 3.0 per cent for the ratio of
Time Temperature the area of the peak due to the plastic additive to that due
(min) (°C) to the internal standard, determined on 6 injections of a
Column 0 - 3.3 100 → 200 reference solution of each plastic additive tested situated in
the middle of the calibration range (e.g. 20 μg/mL).
3.3 - 20 200 → 250
From the calibration curve obtained with the reference
20 - 22.5 250 solutions, calculate the percentage content of plastic additives
in the material to be examined.
22.5 - 23 250 → 270
Limits :
23 - 25 270 – plastic additive 01 : maximum 40 per cent ;
25 - 25.6 270 → 320 – plastic additive 24 : maximum 45 per cent ;
25.6 - 30.6 320 – plastic additive 25 : maximum 45 per cent ;
– plastic additive 26 : maximum 45 per cent ;
Injection port 300
– plastic additive 27 : maximum 45 per cent.
Detection : mass spectrometer as described below ; adjust the Barium : maximum 5 ppm.
detector settings so as to comply with the system suitability Inductively coupled plasma-atomic emission spectrometry
criteria : (2.2.57).
– quadrupole mass spectrometer equipped with an electron Test solution. Ignite 1.0 g of the material to be examined in a
impact ionisation mode (70 eV) ; silica crucible. Take up the residue with 10 mL of hydrochloric
– ion source temperature : 230 °C ; acid R and evaporate to dryness on a water-bath. Take up the
residue with 20 mL of 0.1 M hydrochloric acid.
– acquisition system : performed on full-scan (m/z = 40-350)
Reference solution. A solution containing 0.25 ppm of
and on single-ion monitoring (SIM) modes ;
barium prepared by dilution of barium standard solution
– solvent delay : 2.5 min ; (50 ppm Ba) R with 0.1 M hydrochloric acid.
– mass spectrometer parameters for the fragmentometric Wavelength : use the emission of barium at 455.40 nm, the
mode (SIM) set as follows : spectral background being taken at 455.30 nm.

470 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.0 3.3.4. Sterile plastic containers for human blood

Verify the absence of barium in the hydrochloric acid used. specifications (see 3.1. Materials used for the manufacture of
Cadmium : maximum 0.6 ppm. containers and subsections and 3.3. Containers for human
blood and blood components, and materials used in their
Atomic absorption spectrometry (2.2.23, Method I). manufacture ; transfusion sets and materials used in their
Test solution. Evaporate 10.0 mL of solution S1 to dryness. manufacture ; syringes and subsections).
Take up the residue using 5 mL of a 1 per cent V/V solution Materials other than those described in the Pharmacopoeia
of hydrochloric acid R, filter and dilute the filtrate to 10.0 mL may be used provided that their composition is authorised by
with the same acid. the competent authority and that the containers manufactured
Reference solutions. Prepare the reference solutions using from them comply with the requirements prescribed in this
cadmium standard solution (0.1 per cent Cd) R, diluting with a general chapter.
1 per cent V/V solution of hydrochloric acid R. In normal conditions of use the materials do not release
Source : cadmium hollow-cathode lamp. monomers, or other substances, in amounts likely to be
Wavelength : 228.8 nm. harmful nor do they lead to any abnormal modifications of
Atomisation device : air-acetylene flame. the blood.
Verify the absence of cadmium in the hydrochloric acid used. The containers may contain anticoagulant solutions,
depending on their intended use, and are supplied sterile.
Tin : maximum 20 ppm.
Each container is fitted with attachments suitable for the
Inductively coupled plasma-atomic emission spectrometry intended use. The container may be in the form of a single unit
(2.2.57). or the collecting container may be connected by one or more
Test solution. Dilute solution S1 10-fold with water R tubes to one or more secondary containers to allow separation
immediately before use. of the blood components to be effected within a closed system.
Reference solution. Introduce 2 mL of tin standard solution The outlets are of a shape and size allowing for adequate
(5 ppm Sn) R into a 50 mL flask containing 5 mL of a 20 per connection of the container with the blood-giving equipment.
cent V/V solution of sulfuric acid R and dilute to 50 mL with The protective coverings on the blood-taking needle and on
water R immediately before use. the appendages must be such as to ensure the maintenance
Wavelength : use the emission of tin at 189.99 nm, the spectral of sterility. They must be easily removable but must be
background being taken at 190.10 nm. tamper-evident.
Verify the absence of tin in the sulfuric acid used. The capacity of the containers is related to the nominal
Heavy metals (2.4.8) : maximum 50 ppm. capacity prescribed by the national authorities and to the
appropriate volume of anticoagulant solution. The nominal
To 10 mL of solution S1 add 0.5 mL of phenolphthalein capacity is the volume of blood to be collected in the container.
solution R and then strong sodium hydroxide solution R until The containers are of a shape such that when filled they may
a pale pink colour is obtained. Dilute to 25 mL with water R. be centrifuged.
12 mL of the solution complies with test A. Prepare the
reference solution using lead standard solution (2 ppm Pb) R. The containers are fitted with a suitable device for suspending
or fixing which does not hinder the collection, storage,
ASSAY processing or administration of the blood.
To 0.500 g of the material to be examined add 30 mL of The containers are enclosed in sealed, protective envelopes.
tetrahydrofuran R and heat with stirring on a water-bath in a
fume cupboard for 10 min. The material dissolves completely. CHARACTERS
Add 60 mL of methanol R dropwise with stirring. A granular The container is sufficiently transparent to allow adequate
precipitate of poly(vinyl chloride) is formed. Allow to stand visual examination of its contents before and after the taking
for a few minutes. Continue addition of methanol R until no of the blood and is sufficiently flexible to offer minimum
further precipitation is observed. Transfer to a sintered-glass resistance during filling and emptying under normal
filter (40) (2.1.2), using 3 small quantities of methanol R to aid conditions of use. The container contains not more than 5 mL
transfer and to wash the precipitate. Dry the filter and the of air.
precipitate to constant mass at 60 °C and weigh.
TESTS
Additional tests for sterilised sets are described in general
chapter 3.3.7. Sets for the transfusion of blood and blood Solution S1. Fill the container with 100 mL of a sterile,
components. pyrogen-free 9 g/L solution of sodium chloride R. Close the
container and heat it in an autoclave so that the contents are
maintained at 110 °C for 30 min.
01/2020:30304 If the container to be examined contains an anticoagulant
solution, first empty it, rinse the container with 250 mL of
water for injections R at 20 ± 1 °C and discard the rinsings.
Solution S2. Introduce into the container a volume of water
for injections R corresponding to the intended volume of
3.3.4. STERILE PLASTIC CONTAINERS anticoagulant solution. Close the container and heat it in an
FOR HUMAN BLOOD AND autoclave so that the contents are maintained at 110 °C for
30 min. After cooling, add sufficient water for injections R to
BLOOD COMPONENTS fill the container to its nominal capacity.
Plastic containers for the collection, storage, processing and If the container to be examined contains an anticoagulant
administration of blood and its components are manufactured solution, first empty it and rinse it as indicated above.
from one or more polymers, if necessary with additives. Resistance to centrifugation. Introduce into the container a
The composition and the conditions of manufacture of volume of water R, acidified by the addition of 1 mL of dilute
the containers are registered by the appropriate competent hydrochloric acid R, sufficient to fill it to its nominal capacity.
authorities in accordance with the relevant national legislation Envelop the container with absorbent paper impregnated with
and international agreements. a 1 in 5 dilution of bromophenol blue solution R1 or other
When the composition of the materials of the different parts of suitable indicator and then dried. Centrifuge at 5000 g for
the containers corresponds to the appropriate specifications, 10 min. No leakage perceptible on the indicator paper and no
their quality is controlled by the methods indicated in those permanent distortion occur.

General Notices (1) apply to all monographs and other texts 471