Collaborating with MilliporeSigma to incorporate CCS values

Accurate screening for extractables and leachables (E&Ls) is imperative for consumer safety, no matter the product. Be it a pharmaceutical, an item of food packaging, or a medical device, consumers place their trust in manufacturers to protect them from the thousands of potentially harmful chemicals that can leach into their products. 

Through an exciting collaboration between Waters Corporation and the Life Science Business of MilliporeSigma, cross-collision (CCS) values are referenced on Sigma-Aldrich.com for LC/MS amendable E&L Certified Reference Materials (CRM) and analytical standards. As ion mobility spectrometry (IMS) becomes more routine, CCS values provide an additional identification point, strengthening results for labs and enhancing safety for consumers. 

E&L reference materials that you can trust 

As part of the collaboration, Waters and MilliporeSigma have jointly constructed a comprehensive UPLC-IMS-MS E&L library based on high-quality reference materials. The library can help users screen for a wide array of E&L compounds, with each addition to the library carefully selected to ensure maximum relevance to users. Each reference material also provides users with major identification points including m/z values for product ions, fragment ions and CCS.

Through application of IMS, the rotationally-averaged collision cross-section (CCS) of a given ion can be determined. It is a distinguishing characteristic and provides users with an additional descriptor that can improve confidence in their results. 

We sat down with some of the minds that helped drive this collaboration forward so they could share their insights into how it will support analytical labs and enable greater throughput efficiency. Speaking to us from the Waters team were Mike McCullagh, [Consultant Scientist], Ben MacCreath, [Chemical Materials Business Operations], and Jens Jacobsen, [Sales Specialist] at Waters. From the MilliporeSigma side, we spoke to Coralie Leonard, [Business development, licensing and innovation manager], Dr Matthias Nold, [Product Manager for Reference Materials], and Markus Obkircher, [Director of R&D].

E&L standards are paramount to safety

E&L standards are a rapidly growing area of regulatory screening, driven predominantly by tightening regulations. As our understanding of the materials used in consumer products grows, so does our appreciation of the potentially harmful chemicals humans might be exposed to. 

Waters’ Jens Jacobsen, speaking about E&L standards, said, “For E&L, we’re potentially looking at more than 100,000 potential harmful compounds, and we still don’t know all of them.” 

“The field of E&L is very broad and has still many unknown-unknowns, compounds that are neither detected and nor identified. The reduction of a potential health impact of such substances for end-users is the ultimate goal of this collaboration” MilliporeSigma’s Markus Obkircher added.

Ben MacCreath, shared his perspective on the importance of E&L standards as a Waters expert, “It’s driven by consumer protection. Whether we’re eating, drinking, buying cosmetics, benefiting from a medical device, or taking certain drugs, we always have the potential to expose ourselves to undesired chemicals.”

He went on, “As consumers, we place our trust in the manufacturers and the regulations that govern them, and these manufacturers need to know and show what potential moieties can migrate or leach and assess these. It’s for these goals that accurate libraries are absolutely critical.”

MilliporeSigma’s Coralie Leonard elaborated, “The need for these standards and regulations is also, in part, driven by the increased globalization of supplies. Today, materials can come from multiple places across the world, so to keep the consumer at the end of the line safe, it’s important that countries are harmonized on the regulations and standards.”

CCS: Extending the power of analysis of E&L

Equipped with the E&L library and the use of certified reference materials (CRMs), you can both more effectively screen for potentially harmful compounds and eliminate false positives. 

The E&L library includes verified CCS values for the corresponding MilliporeSigma’s CRMs and analytical standards, allowing users to further probe their data in a more in-depth way. Alongside other intrinsic values, such as the m/z ratio of product ions, fragmentation, and retention times, CCS gives you yet another physical parameter that is intrinsic to the molecule, helping you more easily eliminate potential compound candidates during analysis.

“The way CCS values aren’t dependent on the measuring instrumentation really fills me with confidence. In the reference materials industry, this harmonization is really important and tells me it is perhaps more robust than other values,” Coralie Leonard said.

Waters’ Ben MacCreath continued, “The verified CCS values provide this dual aspect of data cleanliness, which simplifies the information and increases specificity, and also the power of identification, giving you further confidence in your results.” 

Additionally, by having CCS values, labs may validate results faster, ensuring more rapid throughput and overall efficiency. 

Jens Jacobsen from Waters added, “On one hand, with another dimension in the form of CCS, you can reduce false positives, which normally would be an extra cost to an analytical lab as they re-confirm and elucidate. And then, of course, the much greater impact is reducing the risk of false negatives, which might have a catastrophic impact on product safety.”

In a semi-targeted analysis, there are thousands of potential analytes to consider, and the availability of CCS values can simplify this. On this, MilliporeSigma’s Matthias Nold said, “Labs doing E&L analysis need to be really careful not to overlook any contaminants and to efficiently identify unknowns. The CCS values are a useful tool for customers to fulfill these needs. This extra identification point also complements the criteria that MilliporeSigma’s product information displays currently.”

Markus Obkircher summarized, “In other words, the addition of CCS values on our eCommerce platform and product detail pages falls in line with MilliporeSigma’s high standard of quality when it comes to the characterization of products that we are providing to testing laboratories.”

Creating the E&L library

We asked Mike McCullagh about the work that went into calculating the CCS values for MilliporeSigma’s E&L standards.

“It’s an extensive piece of work, but we actually developed a workflow where we acquire non-targeted MS data in both positive and negative ion modes. From that, we measure the precursor ions and adducts and determine the CCS for each species.”

“So, whether you have a protonated or sodiated adduct, you are effectively provided with additional identification descriptors.”

In creating this library, at Waters, we have increased our own E&L UNIFI library content by nearly 10%. These have been produced exclusively as part of the MilliporeSigma collaboration, with further expansions to the library anticipated.

When asked about the benefits it provides to users, Mike added, “Fundamentally, the work is already performed, and all the information about the compounds is provided in the library for their use.”

For this project, the team used the SYNAPT XS High-Resolution Mass Spectrometer, which incorporates ion mobility for workflow efficiency. 

Collaborating for the future

Across almost every industry, collaboration is a cornerstone of success, and E&L is no different. As Markus Obkircher said, “Without collaboration such as this one with Waters, we are simply reinventing the wheel over and over again.”

He went on, “The collaboration between Waters and MilliporeSigma is a really perfect example of an effective relationship. The way our different competencies, facilities and capabilities combine make for an extremely symbiotic result.”

Jens Jacobsen, who has been a member of the collaboration steering committee for the duration of this project, also discussed working with MilliporeSigma.

“When we highlighted the potential benefits of ion mobility to MilliporeSigma, they reacted with great interest. Since they are one of the biggest reference material producers in the world, I suggested we collaborate.”

“Something they were particularly excited about was the impact and value of CCS and the fact that it’s such a stable constant and robust identification point. This was what convinced them to add it to their list of identification points on certain products’ reference page, alongside the conventional reference points such as accurate mass.”

MilliporeSigma’s Markus Obkircher added, “While initially we were looking at buying equipment from Waters, it quickly became apparent that we should broaden the project scope. To provide an effective workflow and value for customers, we have combined Waters’ libraries and MilliporeSigma’s reference material.

On the value of the collaboration, MilliporeSigma’s Coralie Leonard said “There is a great complementation of knowledge between Waters and MilliporeSigma when it comes to the market and understanding our customers’ needs. By working together, it has allowed us to enhance one another’s offerings and really solve customer pain points effectively.”

CCS provides you with unrivaled confidence

With a verified E&L library that includes CCS values, users will have unrivaled confidence in their results. This important development promises to improve workflow efficiency for labs and ultimately contribute to consumer safety.

Learn more about the Extractables and Leachables HRMS library here.

Learn more about MilliporeSigma’s materials offering on https://www.sigmaaldrich.com/standards