Tips & Tricks GPC/SEC: Product Registration and REACH

Daniela Held, PSS Standards Service GmbH, Mainz, Germany

Molecular mass is one of the central parameters required for product registration. Compared to low molar mass substances, the molar mass determination of macromolecular products is more diffi cult because the product is a mixture of chains with different lengths and, therefore, molar masses. Gel permeation chromatography/size-exclusion chromatography (GPC/SEC) is the standard technique to separate macromolecules by size and to measure the complete molar mass distribution as well as the molar mass averages. This technique therefore provides crucial information for product registration, including REACH.

(High) performance comprise widely environment. Of concern, however, are varying molecular weights, structures, and unreacted monomers, oligomers, and compositions. These molecular parameters adjuvants and additives, which are added to infl uence the macroscopic properties of the improve the processability, the stability, and resulting product and are adjusted during the the quality of the fi nal product. Leaching development process. of these (potentially toxic) components can A big advantage of polymers and cause severe (health) issues. Registration macromolecules is that they can be agencies therefore require comprehensive considered as non-toxic, even when characterization with detailed molar mass produced from toxic monomers. As a result information and, for some products, also of their size and the fact that reactive extractables and leachables studies. functional groups are reacting during The molar mass of a product is polymerization, polymers are usually traditionally measured using gel permeation considered to be (bio)chemically inert and chromatography/size-exclusion

Photo Credit: saicle/Shutterstock.com do not pose a threat to humans and the chromatography (GPC/SEC) and the results

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Figure 1: Chromatogram of a polyol with 8+ automatically identifi ed single chains with 1–8 repetition units (compare Table 1 for detailed results).

are of the utmost importance because REACH the molar mass can infl uence which REACH, Registration, Evaluation, registration category will apply for a Authorisation, and Restriction of Chemicals, new product, for example, the molar is an EU regulation that came into force on mass determines whether new products 1 June 2007. It addresses the production of fall into the category “polymer of low chemicals and their impacts on human health concern” (PLC) or if a product is subject for and the environment. For Europe, all polymers registration or not (EU REACH). Accordingly, are exempt from registration and evaluation the generation of detailed and appropriate under REACH. A polymer is here defi ned molar mass data that satisfi es regulatory using three criteria: guidelines is a key component of successful • The molecules must be distributed over a registration. molecular weight range.

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Table 1: Molar mass and weight percentage results for the peaks from Figure 1 show that this Figure 2: Molar mass distribution determined for a typical polymer product. Since Mw is product is a polymer based on REACH criteria above 10000 Da and the fraction below 500/1000 Da are below 2/5%, this product fulfi ls Molar Mass M Content the molar mass requirements for a polymer of low concern. Example Polyol p Comment Polymer? (Da)* (%)

Peak H 200 0.20 R-M, Yes, Less than 50% + Peak G 490 13.4 R-M-M below (3M 1)

Peak F 790 15.7 R-M-M-M

Peak E 1090 14.8 Yes, no individual Peak D 1400 13.3 chain > 50%

Peak C 1810 11.0 Yes, molar mass distribution Peak B 2190 9.30

Peak A 2550 22.3

* Polystyrene equivalents

• The weight percentage of molecules If the molar mass of a product is containing three monomer units or above suffi ciently low, GPC/SEC separations often should exceed 50% (3M+1 rule). show a nice oligomeric profi le as shown in • The weight percentage of any molecule the chromatogram in Figure 1. Identifi cation of the same molecular weight shall not of the single peaks is possible by overlaying exceed 50%. the data with at least one known reference to resolve this into single peaks. This the substance is a polymer according to the material. The single peaks can then be behaviour is very typical for GPC/SEC where defi nition of REACH. Different REACH-like regulations around evaluated with respect to molar mass and for higher molar masses broader peaks are the world have adopted this defi nition, weight percentage. The example shows observed. Polymers of Low Concern although the regularity requirements about a polyol with a molar mass distribution Table 1 shows the numerical results Product registrations often require the Mw the consequences may differ. For example, (criteria 1 met) and eight automatically for the eight identifi ed species and a (weight average molecular weight) and the polymers are not exempt for China-REACH. identifi ed peaks for chains with 1–8+ comparison with REACH polymer defi nition mass fractions below a defi ned molar mass, The preferred method to determine whether a repetition units. For higher molar masses criteria. By comparing the REACH criteria such as 500 or 1000 Da. This is required to substance falls under the defi nition of a polymer (longer chains, 8+ repetition units), the with the GPC/SEC results, it is seen that all classify a product as a PLC. Unfortunately, is GPC/SEC with referral to OECD TG 118 (1). resolution of GPC/SEC was not suffi cient three REACH criteria are met. Consequently, the defi nitions for PLCs in different countries

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can vary as well as the required actions— Please note that there are some general Molar mass distribution determined for a polymer product that does not fulfi l the nevertheless GPC/SEC is able to provide the exclusions for polymers, which are generally Figure 3: molar mass requirements for a polymer of low concern (fraction < 1000 Da is above 5%). required information. not exempted. Cationic or potentially cationic In addition, the measurement uncertainty is displayed, which is quite high here and can be In addition to the area percentage values polymers, high-molecular-weight water improved. for each well separated peak, GPC/SEC absorbing polymers, and polymers that results include the molar mass distribution, degrade, decompose, or depolymerize are which allows Mw to be determined and not eligible for exemption. Reactive groups the required fractions deduced. The molar can also be a problem; as a consequence, mass distribution is obtained from the a polymer would not be exempted from chromatogram when a calibration curve is regulations, even if the mass results indicate available (or more precisely, when the molar that it is a polymer of low concern. mass information for each elution volume In addition, the mass fraction for every is available) (2). As a result of the special molar mass slice (sometimes referred to transformations required in GPC/SEC analysis as slice list) can be required for product it is important to ensure that the results for registration. An additional slice list can easily registration are taken from a true molar mass be created once the molar mass distribution distribution and not from a chromatogram is available. From this slice list the required where only the elution volume is replaced by parameters discussed above can be directly the molar mass (3). determined. Figure 2 shows an example for a sample with a broad molar mass distribution (no resolution Measurement Uncertainty and into single peaks) with graphical molar mass Infl uence of Analytical Parameters distribution and molar mass averages as well Analytical scientists producing data for as the fractions below 500 Da and above product registrations should refl ect on at least highest concern, mass spectrometry (such as Partially related to calibration, the 1000 Da. According to the defi nitions in the two important parts of GPC/SEC analysis. electrospray ionization mass spectrometry measurement uncertainty is the second part US and China, this sample is a polymer of low First, all analysts must make the right [ESI-MS] or matrix-assisted laser desorption– to be reviewed (6). Quality of raw data, concern because the Mw is above 10,000 Da, choice for calibration. GPC/SEC, as a relative ionization [MALDI]) can be a valuable addition analytical conditions, and calibration quality less than 2% are below 500 Da, and less than method, always requires a calibration, either for products where no chemically matching infl uence the results, and the measurement 5% are below 1000 Da. For a polymer of Mw using reference materials or an additional reference materials are available (5). If uncertainty can help to identify random error between 1000 Da and 10,000 Da, the fractions detector that allows the molar mass to be chemically matching reference materials are sources to improve the quality of the data. below 500 Da should be below 10% and measured directly (4). In case of registrations, available, it is recommended to select these Figure 3 shows an example of a molar below 1000 Da 25%, respectively. where the low molar mass parts are of materials over more common materials. mass distribution where the fraction below

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1000 Da is slightly above the 5%. Here data • Determination of result uncertainty review is particularly important because can be important to ensure that the the results lie close to the boundary for a submitted results are of high analytical PLC classifi cation. A more detailed analysis quality. showed that both calibration quality (here: not enough data points in the low molar References mass area) and the quality of raw data 1. OECD Guidelines for the Testing of Chemicals, (here: detector noise) were the main sources Section 1, Physical-Chemical properties Test of uncertainty and should be improved No. 118: Determination of the Number- to gain more confi dence in the data. This Average Molecular Weight and the Molecular is particularly true in such critical cases Weight Distribution of Polymers using Gel where it is important to have a sound, Permeation Chromatography well developed, and documented method, 2. P. Kilz and D. Held, The Column 10(22), 26–30 in addition to the support of additional (2014). methods and data to enable the company 3. P. Kilz and D. Held, in Quantification in LC to make the right decisions and to produce and GC, S. Kromidas and J. Kuss, Eds. (Wiley, trustworthy, precise, and accurate data. 2009). 4. D. Held, The Column 4(6), 18–21 (2008). Summary 5. D. Held, The Column 7(6), 11–14 (2011). • The molar mass of a product determines 6. D. Held and P. Kilz, The Column 8(10), 14–20 which registration category will apply. (2012). GPC/SEC data are therefore crucial for product registrations. Daniela Held studied polymer • Molar mass averages are often not chemistry in Mainz, Germany, and sufficient. Detailed analysis is required, works in the PSS software and especially in the low molar mass area instrument department. She is (toxicity). also responsible for education and • Registration data can only be obtained customer training. from true molar mass distributions where the y-axis w (log M) is correctly E-mail: [email protected] converted. Results for fractions could Website: www.pss-polymer.com otherwise be wrong.

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