ISO 17734-1:2013
(Main)Determination of organonitrogen compounds in air using liquid chromatography and mass spectrometry — Part 1: Isocyanates using dibutylamine derivatives
Determination of organonitrogen compounds in air using liquid chromatography and mass spectrometry — Part 1: Isocyanates using dibutylamine derivatives
ISO 17734-1:2013 gives general guidance for the sampling and analysis of airborne isocyanates in workplace air. When amines and aminoisocyanates are suspected to be emitted (e.g. from thermal degradation of PUR), it is recommended that, in addition to isocyanates, the amines and aminoisocyanates in the air are determined, using DBA and ethyl chloroformate as reagents (see ISO 17734-2). The method is suitable for the determination of a wide range of different isocyanates in both the gas and particle phases. Typical monofunctional isocyanates that can be determined are isocyanic acid (ICA), methyl isocyanate (MIC), ethyl isocyanate (EIC), propyl isocyanate (PIC), butyl isocyanate (BIC), and phenyl isocyanate (PhI). Typical monomeric diisocyanates include 1,6-hexamethylene diisocyanate (HDI), 2,4- and 2,6-toluene diisocyanate (TDI), 4,4'-methylenediphenyl diisocyanate (MDI), 1,5-naphthyl diisocyanate (NDI), isophorone diisocyanate (IPDI), and 4,4'-dicyclohexylmethane diisocyanate (HMDI). Multifunctional isocyanates that can be determined are typically oligomers in polymeric MDI, biuret-, isocyanurate-, and allophanate-adducts, and prepolymeric forms of isocyanates. The instrumental detection limit for aliphatic isocyanates is about 5 nmol/sample and for aromatic isocyanates, it is about 0,2 nmol/sample. For a 15 l air sample, this corresponds to 0,6 ng∙m?3 for HDI and 0,02 ng∙m?3 for TDI. The useful range, for a 5 l air sample, of the method is approximately 0,001 µg∙m?3 to 200 mg∙m?3 for TDI.
Détermination des composés organiques azotés dans l'air par chromatographie liquide et spectrométrie de masse — Partie 1: Isocyanates par les dérivés de la dibutylamine
Določevanje organskih dušikovih spojin v zraku s tekočinsko kromatografijo in masno spektrometrijo - 1. del: Določevanje izocianatov preko derivatov dibutilamina
Ta del standarda ISO 17734 podaja splošne napotke za vzorčenje in analizo izocianatov v zraku na delovnem mestu. Kadar se sumi izločanje aminov in aminoizocianatov (npr. pri termičnem razpadu poliuretana (PUR)), je priporočljivo, da se poleg izocianatov določijo amini in aminoizocianati v zraku, pri čemer se kot reagenta uporabljata dibutilamin (DBA) in etil kloroformiat (standard ISO 17734-2).
Metoda je ustrezna za določanje širokega razpona različnih izocianatov v plinski fazi in fazi delcev. Običajni monofunkcijski izocianati, ki jih je mogoče določiti, so izocianatna kislina (ICA), metil izocianat (MIC), etil izocianat (EIC), propil izocianat (PIC), butil izocianat (BIC) in fenil izocianat (PhI). Med običajne monomerne diizocianate spadajo 1,6-heksametilen-diizocianat (HDI), 2,4- in 2,6-toluen-diizocianat (TDI), 4,4’-metilendifenil-diizocianat (MDI), 1,5-naftil-diizocianat
(NDI), izoforon-diizocianat (IPDI) in 4,4’-dicikloheksilmetan diizocianat (HMDI).
Večfunkcijski izocianati, ki jih je mogoče določiti, so običajno oligomeri v polimernih MDI, biuret-,
izocianurat- in alofanat-adukti ter prepolimerne oblike izocianatov.
Meja detekcije instrumentov za alifatske izocianate je približno 5 nmol/vzorec, za aromatske izocianate pa 0,2 nmol/vzorec. Pri vzorcu zraka s 15 l to ustreza 0,6 ng∙m–3 za HDI
in 0,02 ng∙m–3 za TDI.
The useful range, for a 5 l air sample, of the method is approximately 0,001 μg∙m–3 to 200 mg∙m–3 for TDI.
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INTERNATIONAL ISO
STANDARD 17734-1
Second edition
2013-12-01
Determination of organonitrogen
compounds in air using liquid
chromatography and mass
spectrometry —
Part 1:
Isocyanates using dibutylamine
derivatives
Détermination des composés organiques azotés dans l’air par
chromatographie liquide et spectrométrie de masse —
Partie 1: Isocyanates par les dérivés de la dibutylamine
Reference number
ISO 17734-1:2013(E)
©
ISO 2013
---------------------- Page: 1 ----------------------
ISO 17734-1:2013(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2013
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
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Web www.iso.org
Published in Switzerland
ii © ISO 2013 – All rights reserved
---------------------- Page: 2 ----------------------
ISO 17734-1:2013(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Principle . 1
4 Reagents and materials . 3
5 Preparation of standard solutions . 3
5.1 Reference compounds . 3
5.2 Di-n-butylamine (DBA) derivatives of isocyanates . 4
5.3 DBA derivatives of bulk isocyanates . 5
5.4 DBA derivatives of isocyanates in thermal decomposition products of polyurethane (PUR)
or urea-based resins . 6
5.5 Stability . 6
6 Apparatus . 6
6.2 Flow meter. . 8
6.3 Liquid chromatographic system. . 8
6.4 Ultrasonic bath. . 9
6.5 Evaporator. . 9
7 Air sampling . 9
7.1 Pre-sampling laboratory preparation . 9
7.2 Pre-sampling field preparations . 9
7.3 Collection of air samples .10
7.4 Blanks . .12
7.5 Raw material .12
7.6 Shipment of samples .12
8 Laboratory sample preparation .12
8.1 Sample sequence .12
8.2 Work-up procedure .12
9 Instrumental settings .13
9.1 HPLC program (LC-MS) .13
9.2 HPLC program [LC-chemiluminescent nitrogen detector (LC-CLND)] .13
9.3 Mass spectrometer .13
10 Data handling .14
10.1 Identification .14
10.2 Calibration curves .14
10.3 Quantification .14
11 Interferences .14
12 Determination of performance characteristics.14
12.1 General .14
12.2 Relevant uncertainty contributions and criteria .15
12.3 Assessment of performance characteristics (following the detailed approach in
Reference [18]) .15
Annex A (informative) Performance characteristics .24
Annex B (informative) Examples .26
Annex C (informative) Commercially available products .31
Bibliography .32
© ISO 2013 – All rights reserved iii
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ISO 17734-1:2013(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical Barriers
to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 146, Air quality, Subcommittee SC 2,
Workplace atmospheres.
This second edition of ISO 17734-1 cancels and replaces ISO 17734-1:2006, which has been
technically revised.
ISO 17734 consists of the following parts, under the general title Determination of organonitrogen
compounds in air using liquid chromatography and mass spectrometry:
— Part 1: Isocyanates using dibutylamine derivatives
— Part 2: Amines and aminoisocyanates using dibutylamine and ethyl chloroformate derivatives
iv © ISO 2013 – All rights reserved
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ISO 17734-1:2013(E)
Introduction
Isocyanates have been used in industry for about 50 years. They are commercially important chemicals
mainly used for the production of polyurethane (PUR). In spite of controls to limit exposures, there
are adverse health effects such as asthma, contact dermatitis, and hypersensitivity pneumonitis as
consequences of exposure to isocyanates in some industrial sectors.
The analytical method for the determination of isocyanates in workplace air must be sensitive due to
the high irritation and sensitization properties of isocyanates. Extremely low occupational exposure
limits (OELs) exist in many countries, and concentrations well below the OEL (< 1/100) are often to be
determined. Isocyanates are very reactive and therefore cannot be analysed directly. Derivatization
during sampling is required in order to prevent interfering reactions. Hundreds of different isocyanates
are used in industry, and many more are formed during thermal degradation of PUR. Therefore, high
selectivity of the analytical method is required for accurate results.
The determination of isocyanates in the work environment using di-n-butylamine (DBA) as a reagent and
liquid chromatography-mass spectrometric detection (LC-MS) has been demonstrated to be a robust
method. The development of the method was initiated when difficulties using the “older” methods during
sampling of isocyanates in complex atmospheres were encountered (e.g. thermal decomposition of PUR).
[1][2][3]
The reaction rate between DBA and isocyanates was found to be fast, and high concentrations
can be used to secure instantaneous reactions and eliminate problems with interfering compounds.
[4][5]
Using impinger flasks containing a reagent solution and a filter in series efficiently collects and
[6]
derivatizes isocyanates in both the gas and the particle phase. LC-MS/MS of the isocyanate-DBA
−6 [7]
derivatives enables highly selective and precise determinations down to levels below 10 of the OEL.
Solvent-free sampling can also be performed by using a tube coated with a DBA-impregnated glass fibre
filter followed by an impregnated filter. An impregnation solution containing DBA together with an acid
[8]
is used, and the formed ion pair reduces volatility. DBA remains on the filter even after 8 h of sampling.
Monomeric isocyanates that are formed during thermal decomposition of polymers [typically PUR
and phenol/formaldehyde/urea (PFU) resins], such as isocyanic acid and methyl isocyanate, can
[6][7][8][9][10]
also be determined. Volatile isocyanate-DBA derivatives can be determined using gas
[9]
chromatography-mass spectrometric detection (GC-MS). Using the DBA method and derivatization
with ethyl chloroformate makes simultaneous determinations of amine, aminoisocyanates, and
isocyanates possible, as described in the companion method ISO 17734-2.
For quantification, reference compounds are necessary but are only available for a few monomeric
isocyanates. Most of the isocyanates that are used in industry for the production of PUR can only be
obtained in technical grade mixtures. Many isocyanates that are formed during thermal degradation are
not available and are not easily synthesized. In this method, a nitrogen-sensitive detector has been used for
quantifying isocyanates in reference solutions. This technique has been demonstrated to be a useful tool,
[10][11][12]
together with MS characterization, in greatly facilitating the production of reference solutions.
For quantifying isocyanates in complex mixtures, MS detection appears to be the current best available
detection technique and provides a unique possibility of identifying unknown compounds. This method
has enabled assessment of new areas for which exposure to isocyanates was not known previously and
[6][7][8][9][10][11][12]
has identified new kinds of isocyanates in the work environment.
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INTERNATIONAL STANDARD ISO 17734-1:2013(E)
Determination of organonitrogen compounds in air using
liquid chromatography and mass spectrometry —
Part 1:
Isocyanates using dibutylamine derivatives
1 Scope
This part of ISO 17734 gives general guidance for the sampling and analysis of airborne isocyanates
in workplace air. When amines and aminoisocyanates are suspected to be emitted (e.g. from thermal
degradation of PUR), it is recommended that, in addition to isocyanates, the amines and aminoisocyanates
in the air are determined, using DBA and ethyl chloroformate as reagents (see ISO 17734-2).
The method is suitable for the determination of a wide range of different isocyanates in both the gas and
particle phases. Typical monofunctional isocyanates that can be determined are isocyanic acid (ICA),
methyl isocyanate (MIC), ethyl isocyanate (EIC), propyl isocyanate (PIC), butyl isocyanate (BIC), and
phenyl isocyanate (PhI). Typical monomeric diisocyanates include 1,6-hexamethylene diisocyanate
(HDI), 2,4- and 2,6-toluene diisocyanate (TDI), 4,4’-methylenediphenyl diisocyanate (MDI), 1,5-naphthyl
diisocyanate (NDI), isophorone diisocyanate (IPDI), and 4,4’-dicyclohexylmethane diisocyanate (HMDI).
Multifunctional isocyanates that can be determined are typically oligomers in polymeric MDI, biuret-,
isocyanurate-, and allophanate-adducts, and prepolymeric forms of isocyanates.
The instrumental detection limit for aliphatic isocyanates is about 5 nmol/sample and for aromatic
–3
isocyanates, it is about 0,2 nmol/sample. For a 15 l air sample, this corresponds to 0,6 ng∙m for HDI
–3
and 0,02 ng∙m for TDI.
–3 –3
The useful range, for a 5 l air sample, of the method is approximately 0,001 µg∙m to 200 mg∙m for TDI.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 5725-2, Accuracy (trueness and precision) of measurement methods and results — Part 2: Basic method
for the determination of repeatability and reproducibility of a standard measurement method
ISO 16200-1, Workplace air quality — Sampling and analysis of volatile organic compounds by solvent
desorption/gas chromatography — Part 1: Pumped sampling method
3 Principle
Samples are collected by drawing a known volume of air through a midget impinger flask followed by
–1
a filter. The impinger contains 10 ml of 0,01 mol∙l of DBA in toluene and the filter is a glass fibre filter
with no binder.
Solvent-free sampling can also be performed by drawing air through a tube coated with a DBA-impregnated
glass fibre filter followed by an impregnated filter. An impregnation solution containing DBA together
with acetic acid is used, the ion pair so formed reduces the volatility and enables long-time sampling.
After sampling, deuterium-labelled isocyanate-DBA derivatives (used as internal standard) are added
to the sample solutions. The excess reagent and solvent are evaporated, and the samples are dissolved
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ISO 17734-1:2013(E)
in acetonitrile. The samples are analysed using reversed-phase LC and electrospray (ESP)-MS detection,
monitoring positive ions. Quantification is made by monitoring selected ions. See Figure 1.
Quantification and qualitative determinations can be performed using different LC-MS or
LC-MS/MS techniques. Liquid chromatography-chemiluminescent nitrogen detection (LC-CLND), or
liquid chromatography-ultraviolet detection (LC-UV) for aromatic isocyanates, can be used for the
determination of higher concentrations of isocyanates.
Reference materials can be characterized using LC-MS/CLND. For characterization of volatile compounds,
gas chromatography-thermionic specific detector (GC-TSD) can also be used.
Sampling
Standard solution :
Calibration curve Transfer of sample solution DBA derivatives of diisocyanates,
monoisocyanates, isocyanate
from standard solution and filter media to test tube
adducts and oligomeres
Internal standard, IS:
- Similar in retention time
- Similar in molecular structure
Addition of IS
i.e. aromatic or aliphatic
- Preferably deuterium-labelled
DBA derivative of the isocyanate
- Extraction of analytes
Work-up procedure - Change of solution media
- Enrichment of the analytes
- SIM or MRM of the analytes and IS
Analysis with LC-MS
- Calculation of the area ratio of
the analyte and IS
Evaluation of data
- Comparison between area ratio of
the air sample and calibration plot
Figure 1 — Principle of the described method
2 © ISO 2013 – All rights reserved
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ISO 17734-1:2013(E)
4 Reagents and materials
4.1 DBA reagent.
Analytical grade di-n-butylamine is commercially available.
4.2 Solvents.
The reagent solvent, typically toluene, and other solvents, such as acetonitrile, isooctane, and methanol,
should be of liquid chromatographic quality.
4.3 Formic acid, concentrated formic acid, analytical grade.
4.4 Acetic acid, concentrated acetic acid, analytical grade.
4.5 Sulfuric acid 5 mM, 0,27 ml of concentrated sulfuric acid (98 %) is added to 1 000 ml of water.
4.6 Reagent solution.
In a 1 l volumetric flask, dilute 1,69 ml of DBA in toluene and make up to the mark. The solution is stable
and no special care during storage is necessary.
4.7 Reagent solution, for solvent-free sampler.
–1
4.7.1 Solution 1: 0,74 mol∙l DBA.
Mix 80 ml methanol and 12,5 ml DBA in a 100 ml volumetric flask. Then while stirring, slowly add
4,16 ml of acetic acid to the flask. Finally, add methanol to the flask, and make up to the mark.
–1
4.7.2 Solution 2: 1,5 mol∙l DBA.
Mix 60 ml methanol and 25 ml DBA in a 100 ml volumetric flask. Then while stirring, slowly add 8,32 ml
of acetic acid to the flask. Finally, add methanol to the flask, and make up to the mark.
4.8 HPLC mobile phases.
4.8.1 LC-MS.
The weak mobile phase (mobile phase A) consists of water/acetonitrile (95/5 volume fraction) and
0,05 % formic acid. The strong mobile phase (mobile phase B) consists of water/acetonitrile (5/95
volume fraction) and 0,05 % formic acid. The mobile phases are degassed prior to use.
4.8.2 LC-CLND.
The weak mobile phase (mobile phase C) consists of water/methanol (95/5 volume fraction) and 0,05 %
formic acid. The strong mobile phase (mobile phase D) consists of water/methanol (5/95 volume fraction)
and 0,05 % formic acid. The mobile phases are degassed prior to use.
5 Preparation of standard solutions
5.1 Reference compounds
Reference compounds are necessary for LC-MS determination of isocyanate derivatives. For the
commercially available isocyanates, the DBA derivatives are easily prepared by direct derivatization
with DBA. DBA derivatives for the isocyanates not commercially available can be made from the bulk
© ISO 2013 – All rights reserved 3
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ISO 17734-1:2013(E)
material or from the thermal decomposition of PUR or urea-based resins used at the work place.
Alternatively, standard solutions can be purchased (see Annex C).
5.2 Di-n-butylamine (DBA) derivatives of isocyanates
5.2.1 Preparation of isocyanate-DBA derivatives of commercially available isocyanates
Many frequently used isocyanates are commercially available from companies supplying laboratory
chemicals such as HDI, 2,4-TDI and 2,6-TDI, 4,4’-MDI, 4,4’-HMDI, 1,5-NDI, IPDI, PhI, MIC, EIC, PIC, and
BIC. The purity of the isocyanates varies, and some contain isomers.
Calibration standards are made by spiking accurately weighed amounts or volumes (ca 0,1 mmol) of
–1
isocyanates in 100 ml of isooctane. A 1 ml volume is added to 100 ml of toluene containing 0,01 mol∙l
–1
of DBA (ca 0,01 µmol∙ml of the DBA derivative).
The procedure for the synthesis of derivatives is as follows:
1) Dilute 6 mmol of isocyanate in 2 ml of isooctane.
2) Dissolve 60 mmol of DBA in 20 ml of isooctane.
3) Add the isocyanate solution to the DBA solution dropwise under continuous stirring.
4) Evaporate the reaction mixture to dryness in a rotating evaporator.
5) Dry the residue under vacuum to remove excess DBA.
It is also possible to prepare the isocyanate-DBA derivatives by collecting the thermal degradation
products of the corresponding carbamate esters in an impinger flask containing a DBA solution (as
specified in 5.2.3.3).
5.2.2 Preparation of ICA and MIC-DBA
When urea is thermally degraded, ICA is formed.
Heat an amount of urea (20 mg) to about 300 °C in a glass tube. Collect the degradation products in an
–1
impinger flask containing DBA in toluene (0,5 mol∙l ). Wash the toluene solution containing the ICA-
DBA derivatives with water, whereupon the organic phase is evaporated in a vacuum centrifuge and the
residue is dissolved in methanol. Characterize the solution, as described in 5.2.4.
The same procedure can be applied for preparation of MIC-DBA derivatives, by collecting thermal
degradation products of 1,3-dimethyl urea.
5.2.3 Preparation of deuterium-labelled isocyanate-DBA derivatives
5.2.3.1 Internal standards
For accurate LC-MS quantifications, it is important to use proper internal standards, not only to
compensate for variations during the work-up procedure, but also to compensate for fluctuation in the
MS instrument response. Ideally, each analyte should have its own deuterium-labelled analogue. For
isocyanate-DBA determinations, it is possible to use DBA derivatives of deuterium-labelled isocyanates
or d - and d -DBA derivatives of the isocyanates as internal standards.
9 18
The quality of the quantification is influenced by the number of deuterium substitutions in the internal
standard (less deuterium in the molecule result in higher precision). Having the deuterium on the isocyanate,
and not on the DBA, has advantages when performing structural identification using MS and MS/MS. It is
then possible to distinguish between labelled and non-labelled fragments that originate from the isocyanate
itself. Therefore, the ideal internal standards are the DBA derivatives of the deuterium-labelled isocyanates.
However, they are labour intensive to prepare, and they are only available for a few isocyanates.
4 © ISO 2013 – All rights reserved
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ISO 17734-1:2013(E)
The deuterium-labelled d - and d -DBA derivatives are easy to prepare, and any technical isocyanate
9 18
or thermal degradation product can be derivatized and used as internal standard.
5.2.3.2 DBA derivatives of deuterium-labelled isocyanates
Dissolve a 10 mmol aliquot of the deuterium-labelled corresponding amine in 20 ml of toluene. Thereafter,
–1
add 150 µl pyridine and 40 ml of 5 mol∙l NaOH. Then add 1,5 ml of ethyl chloroformate dropwise under
continuous stirring. After 10 min, the toluene phase is separated, and the solvent is evaporated.
Place the residue containing the formed amine carbamate ester (10 µl) in a glass tube. Heat the tube
–1
to about 300 °C. By connecting the tube to an impinger flask, containing 0,5 mol∙l DBA in toluene, the
formed deuterium-labelled isocyanate is collected as a DBA derivative. Evaporate the solvent, and dissolve
the residue in methanol to an appropriate concentration. Characterize the solution, as described in 5.2.4.
5.2.3.3 d -DBA and d -DBA derivatives of the isocyanates
9 18
Prepare the deuterium-labelled d - and d -DBA derivatives by dissolving accurately weighed amounts
9 18
–1
of the isocyanates in 10 ml of 0,1 mol∙l d -DBA or d -DBA in toluene.
9 18
Prepare the deuterium-labelled derivatives of ICA and MIC by placing 20 mg of urea for ICA and
1,3-dimethyl urea for MIC in a glass tube. Heat the tube to about 300 °C and collect the formed ICA and
–1
MIC in impinger flasks containing 0,1 mol∙l d -DBA or d -DBA in toluene. Evaporate the solutions
9 18
containing the isocyanate d -DBA or d -DBA derivatives to dryness, and dissolve the residues in
9 18
methanol. Characaterize the solution, as described in 5.2.4.
5.2.4 Characterization
The solutions are diluted in methanol to appropriate concentrations and characterized on the LC-MS and
quantified on the LC-CLND. This technique is nitrogen specific and any nitrogen-containing compound
[13][14][15]
can be used as external standard, e.g. caffeine. The technique is used in several applications.
Quantification of volatile isocyanate-DBA derivatives can also be made by using GC-TSD.
5.3 DBA derivatives of bulk isocyanates
5.3.1 Preparation
Technical isocyanates used in industry are typically available in mixtures such as oligomers in polymeric
MDI, biuret-, isocyanurate-, and allophanate-adducts, and prepolymeric forms of isocyanates. These
isocyanates are typically multifunctional.
If product data sheets are available and correct, standard solutions for the technical-grade isocyanates
can be prepared in the same way as described in 5.2.1, by adding a known amount of bulk isocyanate to
a toluene solution of DBA. If
...
SLOVENSKI STANDARD
SIST ISO 17734-1:2015
01-marec-2015
'RORþHYDQMHRUJDQVNLKGXãLNRYLKVSRMLQY]UDNXVWHNRþLQVNRNURPDWRJUDILMRLQ
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Determination of organonitrogen compounds in air using liquid chromatography and
mass spectrometry - Part 1: Isocyanates using dibutylamine derivatives
Détermination des composés organiques azotés dans l'air par chromatographie liquide
et spectrométrie de masse - Partie 1: Isocyanates par les dérivés de la dibutylamine
Ta slovenski standard je istoveten z: ISO 17734-1:2013
ICS:
13.040.30 Kakovost zraka na delovnem Workplace atmospheres
mestu
71.040.50 Fizikalnokemijske analitske Physicochemical methods of
metode analysis
SIST ISO 17734-1:2015 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
---------------------- Page: 1 ----------------------
SIST ISO 17734-1:2015
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SIST ISO 17734-1:2015
INTERNATIONAL ISO
STANDARD 17734-1
Second edition
2013-12-01
Determination of organonitrogen
compounds in air using liquid
chromatography and mass
spectrometry —
Part 1:
Isocyanates using dibutylamine
derivatives
Détermination des composés organiques azotés dans l’air par
chromatographie liquide et spectrométrie de masse —
Partie 1: Isocyanates par les dérivés de la dibutylamine
Reference number
ISO 17734-1:2013(E)
©
ISO 2013
---------------------- Page: 3 ----------------------
SIST ISO 17734-1:2015
ISO 17734-1:2013(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2013
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland
ii © ISO 2013 – All rights reserved
---------------------- Page: 4 ----------------------
SIST ISO 17734-1:2015
ISO 17734-1:2013(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Principle . 1
4 Reagents and materials . 3
5 Preparation of standard solutions . 3
5.1 Reference compounds . 3
5.2 Di-n-butylamine (DBA) derivatives of isocyanates . 4
5.3 DBA derivatives of bulk isocyanates . 5
5.4 DBA derivatives of isocyanates in thermal decomposition products of polyurethane (PUR)
or urea-based resins . 6
5.5 Stability . 6
6 Apparatus . 6
6.2 Flow meter. . 8
6.3 Liquid chromatographic system. . 8
6.4 Ultrasonic bath. . 9
6.5 Evaporator. . 9
7 Air sampling . 9
7.1 Pre-sampling laboratory preparation . 9
7.2 Pre-sampling field preparations . 9
7.3 Collection of air samples .10
7.4 Blanks . .12
7.5 Raw material .12
7.6 Shipment of samples .12
8 Laboratory sample preparation .12
8.1 Sample sequence .12
8.2 Work-up procedure .12
9 Instrumental settings .13
9.1 HPLC program (LC-MS) .13
9.2 HPLC program [LC-chemiluminescent nitrogen detector (LC-CLND)] .13
9.3 Mass spectrometer .13
10 Data handling .14
10.1 Identification .14
10.2 Calibration curves .14
10.3 Quantification .14
11 Interferences .14
12 Determination of performance characteristics.14
12.1 General .14
12.2 Relevant uncertainty contributions and criteria .15
12.3 Assessment of performance characteristics (following the detailed approach in
Reference [18]) .15
Annex A (informative) Performance characteristics .24
Annex B (informative) Examples .26
Annex C (informative) Commercially available products .31
Bibliography .32
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Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical Barriers
to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 146, Air quality, Subcommittee SC 2,
Workplace atmospheres.
This second edition of ISO 17734-1 cancels and replaces ISO 17734-1:2006, which has been
technically revised.
ISO 17734 consists of the following parts, under the general title Determination of organonitrogen
compounds in air using liquid chromatography and mass spectrometry:
— Part 1: Isocyanates using dibutylamine derivatives
— Part 2: Amines and aminoisocyanates using dibutylamine and ethyl chloroformate derivatives
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Introduction
Isocyanates have been used in industry for about 50 years. They are commercially important chemicals
mainly used for the production of polyurethane (PUR). In spite of controls to limit exposures, there
are adverse health effects such as asthma, contact dermatitis, and hypersensitivity pneumonitis as
consequences of exposure to isocyanates in some industrial sectors.
The analytical method for the determination of isocyanates in workplace air must be sensitive due to
the high irritation and sensitization properties of isocyanates. Extremely low occupational exposure
limits (OELs) exist in many countries, and concentrations well below the OEL (< 1/100) are often to be
determined. Isocyanates are very reactive and therefore cannot be analysed directly. Derivatization
during sampling is required in order to prevent interfering reactions. Hundreds of different isocyanates
are used in industry, and many more are formed during thermal degradation of PUR. Therefore, high
selectivity of the analytical method is required for accurate results.
The determination of isocyanates in the work environment using di-n-butylamine (DBA) as a reagent and
liquid chromatography-mass spectrometric detection (LC-MS) has been demonstrated to be a robust
method. The development of the method was initiated when difficulties using the “older” methods during
sampling of isocyanates in complex atmospheres were encountered (e.g. thermal decomposition of PUR).
[1][2][3]
The reaction rate between DBA and isocyanates was found to be fast, and high concentrations
can be used to secure instantaneous reactions and eliminate problems with interfering compounds.
[4][5]
Using impinger flasks containing a reagent solution and a filter in series efficiently collects and
[6]
derivatizes isocyanates in both the gas and the particle phase. LC-MS/MS of the isocyanate-DBA
−6 [7]
derivatives enables highly selective and precise determinations down to levels below 10 of the OEL.
Solvent-free sampling can also be performed by using a tube coated with a DBA-impregnated glass fibre
filter followed by an impregnated filter. An impregnation solution containing DBA together with an acid
[8]
is used, and the formed ion pair reduces volatility. DBA remains on the filter even after 8 h of sampling.
Monomeric isocyanates that are formed during thermal decomposition of polymers [typically PUR
and phenol/formaldehyde/urea (PFU) resins], such as isocyanic acid and methyl isocyanate, can
[6][7][8][9][10]
also be determined. Volatile isocyanate-DBA derivatives can be determined using gas
[9]
chromatography-mass spectrometric detection (GC-MS). Using the DBA method and derivatization
with ethyl chloroformate makes simultaneous determinations of amine, aminoisocyanates, and
isocyanates possible, as described in the companion method ISO 17734-2.
For quantification, reference compounds are necessary but are only available for a few monomeric
isocyanates. Most of the isocyanates that are used in industry for the production of PUR can only be
obtained in technical grade mixtures. Many isocyanates that are formed during thermal degradation are
not available and are not easily synthesized. In this method, a nitrogen-sensitive detector has been used for
quantifying isocyanates in reference solutions. This technique has been demonstrated to be a useful tool,
[10][11][12]
together with MS characterization, in greatly facilitating the production of reference solutions.
For quantifying isocyanates in complex mixtures, MS detection appears to be the current best available
detection technique and provides a unique possibility of identifying unknown compounds. This method
has enabled assessment of new areas for which exposure to isocyanates was not known previously and
[6][7][8][9][10][11][12]
has identified new kinds of isocyanates in the work environment.
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SIST ISO 17734-1:2015
INTERNATIONAL STANDARD ISO 17734-1:2013(E)
Determination of organonitrogen compounds in air using
liquid chromatography and mass spectrometry —
Part 1:
Isocyanates using dibutylamine derivatives
1 Scope
This part of ISO 17734 gives general guidance for the sampling and analysis of airborne isocyanates
in workplace air. When amines and aminoisocyanates are suspected to be emitted (e.g. from thermal
degradation of PUR), it is recommended that, in addition to isocyanates, the amines and aminoisocyanates
in the air are determined, using DBA and ethyl chloroformate as reagents (see ISO 17734-2).
The method is suitable for the determination of a wide range of different isocyanates in both the gas and
particle phases. Typical monofunctional isocyanates that can be determined are isocyanic acid (ICA),
methyl isocyanate (MIC), ethyl isocyanate (EIC), propyl isocyanate (PIC), butyl isocyanate (BIC), and
phenyl isocyanate (PhI). Typical monomeric diisocyanates include 1,6-hexamethylene diisocyanate
(HDI), 2,4- and 2,6-toluene diisocyanate (TDI), 4,4’-methylenediphenyl diisocyanate (MDI), 1,5-naphthyl
diisocyanate (NDI), isophorone diisocyanate (IPDI), and 4,4’-dicyclohexylmethane diisocyanate (HMDI).
Multifunctional isocyanates that can be determined are typically oligomers in polymeric MDI, biuret-,
isocyanurate-, and allophanate-adducts, and prepolymeric forms of isocyanates.
The instrumental detection limit for aliphatic isocyanates is about 5 nmol/sample and for aromatic
–3
isocyanates, it is about 0,2 nmol/sample. For a 15 l air sample, this corresponds to 0,6 ng∙m for HDI
–3
and 0,02 ng∙m for TDI.
–3 –3
The useful range, for a 5 l air sample, of the method is approximately 0,001 µg∙m to 200 mg∙m for TDI.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 5725-2, Accuracy (trueness and precision) of measurement methods and results — Part 2: Basic method
for the determination of repeatability and reproducibility of a standard measurement method
ISO 16200-1, Workplace air quality — Sampling and analysis of volatile organic compounds by solvent
desorption/gas chromatography — Part 1: Pumped sampling method
3 Principle
Samples are collected by drawing a known volume of air through a midget impinger flask followed by
–1
a filter. The impinger contains 10 ml of 0,01 mol∙l of DBA in toluene and the filter is a glass fibre filter
with no binder.
Solvent-free sampling can also be performed by drawing air through a tube coated with a DBA-impregnated
glass fibre filter followed by an impregnated filter. An impregnation solution containing DBA together
with acetic acid is used, the ion pair so formed reduces the volatility and enables long-time sampling.
After sampling, deuterium-labelled isocyanate-DBA derivatives (used as internal standard) are added
to the sample solutions. The excess reagent and solvent are evaporated, and the samples are dissolved
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in acetonitrile. The samples are analysed using reversed-phase LC and electrospray (ESP)-MS detection,
monitoring positive ions. Quantification is made by monitoring selected ions. See Figure 1.
Quantification and qualitative determinations can be performed using different LC-MS or
LC-MS/MS techniques. Liquid chromatography-chemiluminescent nitrogen detection (LC-CLND), or
liquid chromatography-ultraviolet detection (LC-UV) for aromatic isocyanates, can be used for the
determination of higher concentrations of isocyanates.
Reference materials can be characterized using LC-MS/CLND. For characterization of volatile compounds,
gas chromatography-thermionic specific detector (GC-TSD) can also be used.
Sampling
Standard solution :
Calibration curve Transfer of sample solution DBA derivatives of diisocyanates,
monoisocyanates, isocyanate
from standard solution and filter media to test tube
adducts and oligomeres
Internal standard, IS:
- Similar in retention time
- Similar in molecular structure
Addition of IS
i.e. aromatic or aliphatic
- Preferably deuterium-labelled
DBA derivative of the isocyanate
- Extraction of analytes
Work-up procedure - Change of solution media
- Enrichment of the analytes
- SIM or MRM of the analytes and IS
Analysis with LC-MS
- Calculation of the area ratio of
the analyte and IS
Evaluation of data
- Comparison between area ratio of
the air sample and calibration plot
Figure 1 — Principle of the described method
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4 Reagents and materials
4.1 DBA reagent.
Analytical grade di-n-butylamine is commercially available.
4.2 Solvents.
The reagent solvent, typically toluene, and other solvents, such as acetonitrile, isooctane, and methanol,
should be of liquid chromatographic quality.
4.3 Formic acid, concentrated formic acid, analytical grade.
4.4 Acetic acid, concentrated acetic acid, analytical grade.
4.5 Sulfuric acid 5 mM, 0,27 ml of concentrated sulfuric acid (98 %) is added to 1 000 ml of water.
4.6 Reagent solution.
In a 1 l volumetric flask, dilute 1,69 ml of DBA in toluene and make up to the mark. The solution is stable
and no special care during storage is necessary.
4.7 Reagent solution, for solvent-free sampler.
–1
4.7.1 Solution 1: 0,74 mol∙l DBA.
Mix 80 ml methanol and 12,5 ml DBA in a 100 ml volumetric flask. Then while stirring, slowly add
4,16 ml of acetic acid to the flask. Finally, add methanol to the flask, and make up to the mark.
–1
4.7.2 Solution 2: 1,5 mol∙l DBA.
Mix 60 ml methanol and 25 ml DBA in a 100 ml volumetric flask. Then while stirring, slowly add 8,32 ml
of acetic acid to the flask. Finally, add methanol to the flask, and make up to the mark.
4.8 HPLC mobile phases.
4.8.1 LC-MS.
The weak mobile phase (mobile phase A) consists of water/acetonitrile (95/5 volume fraction) and
0,05 % formic acid. The strong mobile phase (mobile phase B) consists of water/acetonitrile (5/95
volume fraction) and 0,05 % formic acid. The mobile phases are degassed prior to use.
4.8.2 LC-CLND.
The weak mobile phase (mobile phase C) consists of water/methanol (95/5 volume fraction) and 0,05 %
formic acid. The strong mobile phase (mobile phase D) consists of water/methanol (5/95 volume fraction)
and 0,05 % formic acid. The mobile phases are degassed prior to use.
5 Preparation of standard solutions
5.1 Reference compounds
Reference compounds are necessary for LC-MS determination of isocyanate derivatives. For the
commercially available isocyanates, the DBA derivatives are easily prepared by direct derivatization
with DBA. DBA derivatives for the isocyanates not commercially available can be made from the bulk
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material or from the thermal decomposition of PUR or urea-based resins used at the work place.
Alternatively, standard solutions can be purchased (see Annex C).
5.2 Di-n-butylamine (DBA) derivatives of isocyanates
5.2.1 Preparation of isocyanate-DBA derivatives of commercially available isocyanates
Many frequently used isocyanates are commercially available from companies supplying laboratory
chemicals such as HDI, 2,4-TDI and 2,6-TDI, 4,4’-MDI, 4,4’-HMDI, 1,5-NDI, IPDI, PhI, MIC, EIC, PIC, and
BIC. The purity of the isocyanates varies, and some contain isomers.
Calibration standards are made by spiking accurately weighed amounts or volumes (ca 0,1 mmol) of
–1
isocyanates in 100 ml of isooctane. A 1 ml volume is added to 100 ml of toluene containing 0,01 mol∙l
–1
of DBA (ca 0,01 µmol∙ml of the DBA derivative).
The procedure for the synthesis of derivatives is as follows:
1) Dilute 6 mmol of isocyanate in 2 ml of isooctane.
2) Dissolve 60 mmol of DBA in 20 ml of isooctane.
3) Add the isocyanate solution to the DBA solution dropwise under continuous stirring.
4) Evaporate the reaction mixture to dryness in a rotating evaporator.
5) Dry the residue under vacuum to remove excess DBA.
It is also possible to prepare the isocyanate-DBA derivatives by collecting the thermal degradation
products of the corresponding carbamate esters in an impinger flask containing a DBA solution (as
specified in 5.2.3.3).
5.2.2 Preparation of ICA and MIC-DBA
When urea is thermally degraded, ICA is formed.
Heat an amount of urea (20 mg) to about 300 °C in a glass tube. Collect the degradation products in an
–1
impinger flask containing DBA in toluene (0,5 mol∙l ). Wash the toluene solution containing the ICA-
DBA derivatives with water, whereupon the organic phase is evaporated in a vacuum centrifuge and the
residue is dissolved in methanol. Characterize the solution, as described in 5.2.4.
The same procedure can be applied for preparation of MIC-DBA derivatives, by collecting thermal
degradation products of 1,3-dimethyl urea.
5.2.3 Preparation of deuterium-labelled isocyanate-DBA derivatives
5.2.3.1 Internal standards
For accurate LC-MS quantifications, it is important to use proper internal standards, not only to
compensate for variations during the work-up procedure, but also to compensate for fluctuation in the
MS instrument response. Ideally, each analyte should have its own deuterium-labelled analogue. For
isocyanate-DBA determinations, it is possible to use DBA derivatives of deuterium-labelled isocyanates
or d - and d -DBA derivatives of the isocyanates as internal standards.
9 18
The quality of the quantification is influenced by the number of deuterium substitutions in the internal
standard (less deuterium in the molecule result in higher precision). Having the deuterium on the isocyanate,
and not on the DBA, has advantages when performing structural identification using MS and MS/MS. It is
then possible to distinguish between labelled and non-labelled fragments that originate from the isocyanate
itself. Therefore, the ideal internal standards are the DBA derivatives of the deuterium-labelled isocyanates.
However, they are labour intensive to prepare, and they are only available for a few isocyanates.
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The deuterium-labelled d - and d -DBA derivatives are easy to prepare, and any technical isocyanate
9 18
or thermal degradation product can be derivatized and used as internal standard.
5.2.3.2 DBA derivatives of deuterium-labelled isocyanates
Dissolve a 10 mmol aliquot of the deuterium-labelled corresponding amine in 20 ml of toluene. Thereafter,
–1
add 150 µl pyridine and 40 ml of 5 mol∙l NaOH. Then add 1,5 ml of ethyl chloroformate dropwise under
continuous stirring. After 10 min, the toluene phase is separated, and the solvent is evaporated.
Place the residue containing the formed amine carbamate ester (10 µl) in a glass tube. Heat the tube
–1
to about 300 °C. By connecting the tube to an impinger flask, containing 0,5 mol∙l DBA in toluene, the
formed deuterium-labelled isocyanate is collected as a DBA derivative. Evaporate the solvent, and dissolve
the residue in methanol to an appropriate concentration. Characterize the solution, as described in 5.2.4.
5.2.3.3 d -DBA and d -DBA derivatives of the isocyanates
9 18
Prepare the deuterium-labelled d - and d -DBA derivatives by dissolving accurately weighed amounts
9 18
–1
of the isocyanates in 10 ml of 0,1 mol∙l d -DBA or d -DBA in toluene.
9 18
Prepare the deuterium-labelled derivatives of ICA and MIC by placing 20 mg of urea for ICA and
1,
...
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