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Techniques & Tools Capillary Electrophoresis, Mass Spectrometry, Gas Chromatography, Liquid Chromatography

Is CE-MS in Your Toolbox?

In March 2015, I attended the inaugural Analytical Technologies Europe conference in Berlin. Wassim Nasahbeh presented the opening lecture in which he explained that it can easily take up to 30 years for technologies to make it from initial academic publication until they become an accepted standard in industry. This made me think that it is close to 30 years since on-line hyphenation of capillary electrophoresis (CE) and mass spectrometry (MS) was first published. So, where does CE-MS stand today?

In academic research, CE-MS is definitely an established technique, with many research groups around the world using it in very diverse application areas. In today’s industrial laboratories, however, CE-MS is applied only occasionally. But why?

Analytical chemists who are not familiar with CE often claim that it is not robust. Surprisingly, most of these people are unaware of the fact that CE is at the heart of the DNA sequencers that elucidated the human genome with unsurpassed accuracy and speed. Currently, CE is also well established and widely used in biopharma. In the last decade, CE has become a gold standard in monoclonal antibody analysis and is applied routinely from product development to release testing.

Published wide-scale interlaboratory studies have demonstrated robustness, efficacy, specificity and reliability of protein CE methods, which convinces the drug regulation authorities that it is up to the mark. Today, there are ready-to-use CE methods and kits on the market to evaluate protein charge heterogeneity, size distribution, and glycan profiles. Moreover, similar CE methods for the analysis of inorganic ions, low-molecular weight drugs, chiral compounds, and DNA show the enormous versatility of the technique outside of the protein field. Today, we can safely say that we have busted the lack of robustness myth!

So, what is holding back wider application of CE-MS? In my view, there are three important reasons for its narrow take up. First, CE is a younger sibling in the separation methodologies family. Consequently, like in every family, it had to first prove itself extensively and find the areas in which it excelled over its older brothers and sisters before it was considered a suitable alternative. This eventually happened in the DNA and biopharma fields, but it took a number of years. Simultaneously and quickly, its older brother liquid chromatography (LC) also developed in the protein field, because it provides a reasonable alternative for companies as they already have the equipment and knowledge.

Another factor is the compatibility of CE methods with MS detection. When the current gold standard CE methods were first developed, MS compatibility was not a priority. This means it can be difficult to make slight modifications to enable MS coupling. Significant redevelopment and validation often is required, which industrial laboratories are reluctant to do. In contrast, LC and GC methods are often easily transferable to MS detection with only minor adaptation of the conditions.

Finally, CE-MS interfacing is technologically more challenging than LC- or GC-MS interfacing, with only two commercial solutions available today. Unfortunately, of the two, the one with the longest and best track record (20 years) is not a universal solution and can only be used in combination with two mass spectrometer brands. The second interface solution offers broader compatibility; however, it only became available last year and must enter the proving grounds.

So what about the future of CE-MS? Currently, due to the success of standalone CE, CE-MS methods are in high demand. Consequently, vendors, industry, and academics have put great effort in creating the required methods and showing their robustness. The first interlaboratory study on CE-MS is complete and the results are very encouraging. There has also been a renewed interest in technological developments over the last few years, which will definitely help to push CE-MS forward even more. In my view, with the current momentum and investments made, CE-MS has a very healthy future indeed.

Read more, four gurus and I discuss the past and future of CE-MS in more detail.

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About the Author
Rob Haselberg

“Although I apply several other technologies in my research, CE-MS is my main approach. It often provides information that cannot be obtained with any other technology,” says Rob, senior post-doctoral researcher at the VU University Amsterdam, where his research is directed at characterizing biomacromolecular compounds. CE-MS has undergone positive development over the last few years, he explains. “CE-MS was mainly used by academics, but today I am in regular contact with companies that are starting to use (or are planning to use) CE-MS in their laboratories. I am able to share my knowledge with them and in return I get a good insight of the research questions that drive them.”

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