LCGC’s 2018 Emerging Leader Award in Chromatography Winner: Zachary S. Breitbach

Zachary S. Breitbach, the 2018 winner of the LCGC Emerging Leader in Chromatography award, received his PhD in 2010 from the University of Texas at Arlington (UTA). Subsequently, he worked as a research scientist at UTA while simultaneously aiding in the launch of AZYP Separations and Analytics, a chromatographic materials company. Currently, he is a senior scientist at AbbVie. Breitbach has already made important contributions to both high performance liquid chromatography (HPLC) and gas chromatography (GC). In GC, he played a fundamental role in the development, synthesis, characterization, and utilization of highly thermally stable, high viscosity ionic liquids as new GC stationary phases. Two of the ionic liquids he developed were subsequently commercialized. In HPLC, his work covers enantiomeric separations, hydrophilic interaction chromatography (HILIC), ultrafast and high efficiency separations, supercritical and subcritical fluid separations, core–shell bonded phases, and interfacing HPLC to paired ion electrospray ionization (PIESI) mass spectrometry. Here, he discusses how his career got started, his goals for the future, and more.

Where or how did your interest in analytical chemistry begin?

My undergraduate research with Professor Karen Glover and Professor Diana Malone at Clarke College dealt with asymmetric synthesis and required many enantiomeric excess measurements by HPLC. It was this early work that sparked my interest in stereochemistry and separations. The capability of the column to separate so many chemical species and even differentiate enantiomers and the precision of the instrument really amazed me. Entering the graduate program at Iowa State, I was still considering an organic chemistry path, but after interviewing with Professor Daniel W. Armstrong I was sure analytical and separations science was truly my major interest. Joining Professor Armstrong's research group, though it involved a move across the country, was one of the best decisions I ever made.

Your research covers multiple areas of separation science, including HPLC, GC, and capillary electrophoresis (CE) to SFC, HILIC, and MS. Is there one technique you feel more drawn to work with or do you enjoy the challenge of working in many areas of chromatography?

My earliest graduate work involved GC separations and column development, and I always enjoy working with GC because of its maturity, ease of use, and robustness. Yet, it is HPLC that I find most enjoyable. Outside of the analytical balance, HPLC is the most important and most used analytical tool. With all the different modes of HPLC, and the plethora of column choices, it is an exciting challenge each time a different technique or method is required. I also enjoy the many recent advancements in HPLC, including moving to faster separations and columns with higher plate numbers, as well as instrument developments that are always necessary to keep pace with the emerging column technologies. Overall, I have been very fortunate to work in a variety of areas, and I always recommend that young scientists try to do the same. The more techniques you know, the better equipped you will be when you need to solve that next important research problem.

You have done significant work on the development of cyclofructan-based chiral stationary phases. How did that project get started? What were the biggest challenges? What benefits does it bring to the field?

In 2007, I was wandering around a poster session when the cyclic oligosaccharide structure caught my eye. One of the biggest initial challenges was getting the material. Eventually I made contact with Dr. Mari (Yasuda) Hara, of Mitsubishi Chemical Corporation, who very kindly supplied me with some pure cyclofructan 6 and a mixture enriched in cyclofructan 7. Initial attempts were made using cyclofructan derivatives as chiral GC phases, which did not work well. Next, a sulfated version was used very successfully for enantioselective CE. The biggest impact was the use of native cyclofructans as HILIC HPLC selectors and derivatives of cyclofructans as chiral HPLC selectors. Finding the proper derivative and immobilization chemistry, and gaining a mechanistic understanding of cyclofructan phases were all exciting challenges, but in the end seeing important commercial columns being used worldwide has been very rewarding.

What prompted your research into the development, synthesis, characterization, and utilization of highly thermally stable, high viscosity ionic liquids as new GC stationary phases?

Following the research of Professor Jared Anderson and Professor Armstrong on nitrogen-based ionic liquids (ILs), I took a different approach and synthesized and evaluated phosphonium-based ILs. Phosphonium-based ILs have different degradation pathways compared to nitrogen-based ILs and typically exhibit higher thermal stabilities. That benefit, plus the unique selectivity of phosphonium-based IL GC columns, has led to some useful separations of residual solvents and petrochemical mixtures, and the phosponium-based IL phases have proven to be important orthogonal phases for multidimensional separations.

Can you tell us about the development of paired-ion electrospray ionization (PIESI)-MS?

The PIESI-MS technique is one of my favorites, for two reasons. First, because it is such a simple technique that almost always gives increased sensitivity for anionic analytes in addition to other benefits. And second, because it involved collaborative efforts with three of the most influential analytical researchers in my career: Professor Armstrong, Professor Purnendu “Sandy” Dasgupta, and Professor Kevin Schug. Early PIESI work by Professor Dasgupta focused on sensitive perchlorate detection. At the time, we were developing a large number of multicationic ILs, which turned out to be perfect candidates for broad use of PIESI. During this time PIESI was applied to the detection of mono-, di-, and trivalent anions including inorganics, nucleotides, bisphosphonates, phospholipids, pesticides, and even metal complexes, all of which showed orders of magnitude sensitivity enhancements compared to detection in negative-ion mode. Finally, in collaboration with Professor Schug we were able to elucidate the mechanism of sensitivity enhancement for PIESI. A detailed account of the evolution of PIESI-MS can be read in Mass Spectrometry Reviews (1).

Some of your work also led to your role as chief scientific consultant at AZYP, LLC. What did you learn from that position?

There is so much that can be learned working in the fast-paced environment of a new small business. In my particular role, I got to not only learn and refine commercial aspects of column manufacturing (such as scaling up processes, setting specifications, and ensuring reproducible, valid, and robust manufacturing), but also learned about marketing, grantsmanship, and finances. Working with a small business is difficult, but very rewarding if you work hard enough. Though I am not working with AZYP anymore, I certainly have fond memories of the triumphs and tribulations and it’s very exciting to see research come to fruition in the form of impactful commercial products.

What research are you most proud of thus far?

When I think of all the fun projects and collaborations, the one that stands out the most is the work with high-efficiency chiral phases. First, it is probably the most disruptive technology for chiral separations in 10 years or more, and second, at the start of the project I was told it wouldn’t work. Of the two high-efficiency approaches (sub-2-µm and superficially porous particles [SPPs]), I am particularly proud of the SPP-based chiral phases. I had wanted to evaluate SPP-based brush-type chiral stationary phases for several years before I was finally able to get ahold of some unmodified SPPs. Once the SPP material was in hand, there were many challenges in the surface coverage and packing. But persistence and hard work (thank you Daniel Spudeit, Maressa Dolzan, Darshan Patel, Farooq Wahab, and Chandan Barhate) and support from Professor Armstrong paid off. These new columns transformed chiral separations from what was once a long development and run time to shorter screening procedures and possibly extremely fast analyses. For more information on high-efficiency and high-throughput chiral separations see reference 2.

You are currently working in industry. What kind of work are you doing? How is that position different from your previous roles? What new challenges are you presented with?

My current role is to function as an analytical lead in drug product development. Generally speaking, I am responsible for good manufacturing practice (GMP) testing of active pharmaceutical ingredients (API) and drug products (DP), which requires development of proper analytical methods, stability assessments, setting specifications, and supporting formulation. In addition, I am involved in new technology evaluations and development initiatives. At times, what I do now seems very different (especially the level of regulation in a GMP setting versus an academic setting), but it also seems somewhat similar. In both roles, I am faced with analytical challenges. The challenges are perhaps more fundamental in academia and more applied in industry. Either way, the goal is to solve problems. Technically speaking, some of the new challenges include more difficult and complex compound structures to deal with (from a separations perspective), more concern with impurities, and as a whole, working with a much larger group where cross-functional communication is key to success. One thing I have learned is that no matter what type of career choice you make, as long as you work hard, work fair, and have fun, you will enjoy what you’re doing.

Your work has been published a lot (about 70 articles) and you have given 35 oral and 70 poster presentations at national and international conferences. How do you balance your work demands with your personal life? How important is it to you to continue to share your knowledge with the broader scientific community?

Good research results must be shared to competitively advance science. Additionally, if you are an expert in a field or have knowledge that might help someone’s work, I have found that is far more rewarding to share knowledge than the keep it to yourself. After all, I didn’t get a large number of publications without collaboration.

When it comes to work–life balance, there are a few tricks. First, work hard, play hard: I find time every day and most weekends to spend with my family. Second, don’t sleep (well, don’t sleep too much): after the children are in bed and the dogs are walked there is usually time to squeeze in a bit more work. Finally, have good support: I’m a lucky guy here. I have a hard-working wife who manages our personal life including three children (one of which is a newborn). She has really made this possible (thank you, Kelly).

What do you plan to focus on next? Is there one big problem in separation science that you really want to tackle?

A few things I’d like to dive into are process analytical technologies, real-time monitoring of reactions, and point-of-use analytical testing. SFC and two-dimensional (2D)-LC are attractive techniques to further advance for stability indicating methods and impurity identification. Finally, improved techniques for sample prep and analysis of more difficult analytes (such as prodrugs and biologics) are needed.

References

1. Z.S. Breitbach, A. Berthod, K. Huang, and D.W. Armstrong, Mass Spectrometry Reviews35, 201–218 (2016).
2. D.C. Patel, M.F. Wahab, D.W. Armstrong, and Z.S. Breitbach, JCA1467, 2–18 (2016).