Technology Forum: LC–MS

With acetonitrile running low and environmental concerns more important than ever, the challenges facing practitioners of LC–MS in 2009 are unlike those that have come before. And with the ever-present desire to get more sensitive results faster, the daily work of analytical chemists and technicians alike can be daunting indeed.

Joining us for this discussion are Michael P. Balogh of Waters Corporation; Mark Garner of Applied Biosystems; Michael McGinley of Phenomenex; and Jonathan McNally and Lester Taylor of Thermo Fisher Scientific.

What trends do you see emerging in LC–MS?

Balogh:Today’s higher resolution accurate mass capabilities are encouraging wider spread use but we are also seeing closer alignment of quantitation and qualification information through better utility in the software – fewer mouse clicks to derive a more succinct answer. A significant continued transition away from the mass spectrometer’s origins as a qualitative device to use as a comprehensive detector. This trend is perhaps best illustrated by the recent introduction of simultaneous MRM and full-scan acquisitions. The practitioner then has the ability to locate and remedy sources of ion suppression occurring at the same retention time as the analyte of interest.

Garner: Clearly, the LC–MS market is changing from simply selling stand alone instruments to selling total solution systems - software, application methods, etc. To paraphrase Lance Armstrong, "It's not about the box" anymore.

McGinley: As in past years, the main focus of growth in LC–MS revolves around groups working on application development. New LC–MS methods to analyze increasingly more difficult samples continue to be the “hot topic” in publications and at meetings. Also, many groups are coupling automated sample preparation and high-throughput chromatography to take full advantage of the data acquisition speed and computational power that the newest generation of MS instruments offer.

McNally and Taylor: The biggest trend in LC–MS is the use of high resolution and accurate mass enabled instruments becoming easier to use and therefore being widely adopted into routine analysis.

What is the future of LC–MS?

Balogh:It’s always an interesting exercise to look back years from now to see how we did answering such questions. Clearly our vision is constrained somewhat by what we use today – for instance, analytes ionize best by ESI when they are more basic than the solvent. We often make condensed phase assumptions since we use LC so well and ESI ionizes something like 80% of the samples. MS will certainly become even more widely used as it becomes easier and more utilitarian. For instance, when analyses are less reliant on sample prep by using direct sample probes such as ASAP (atmospheric solid analysis probe). Switching between LC and GC is making a return because the technology is now in place to ensure performance of either is not sacrificed as opposed to years ago when instruments were dedicated to narrow uses to get optimum performance.

Garner:I think the clearest trend in LC-MS is the development of "turnkey" applications for clinical research, including peptide-based protein assays, and "applied" assays for food and water testing, etc.

McGinley:It is clear that application development will continue to be the key for LC–MS to expand into new markets and applications. Improvements in ESI interfaces will continue to provide new application areas where MS can be used, and MS systems will continue to improve in sensitivity and speed, further increasing its utility for LC–MS applications.

McNally and Taylor:The future of LC–MS is offering complete integrated solutions including hardware and software for particular markets such as clinical diagnostics, environmental, and food safety. This allows the capabilities of mass spectrometry to be applied to new and growing market applications which have not previously used LC–MS.

What is the LC–MS application area that you see growing the fastest?

Balogh:Clearly accurate mass. High-speed electronics and more stable, robust instruments are coupled with more efficient ion sources which in turn encourage a wider adoption of what might have been considered prohibitively difficult technology a few years ago.

Garner:The FDA "MIST" guidelines are driving a big increase in metabolite identification testing. It's still an area in a state of flux, and of course, MetID is something pharma companies have always done. But this is an area of increased interest.

McGinley:Food and beverage testing as well as environmental testing are areas where there appears to be a lot of growth. Groups are moving to LC–MS to take advantage of the improved sensitivity as well as the positive identity information that LC–MS provides versus older LC-UV and GC methods. LC–MS is also seeing growth in the neutraceutical/ food supplement market as government regulation is enforcing improved quality control methodology on that industry. With the growing concern about global food safety, we are already seeing a dramatic growth in analytical testing of food products (melamine testing for example) using LC–MS and that trend should continue in the near future.

McNally and Taylor:Several areas of growth in both research and applied markets. For example, protein/peptide quantitation is a rapidly growing area of research. In additional we are seeing increasing adoption of LC–MS in almost every industry: pharmaceutical, clinical diagnostics, environmental, food safety, and forensic.

What obstacles stand in the way of LC–MS development?

Balogh:One area, which has plagued all manufacturers from the beginning, is the cost of the vacuum system. Look at the number and placement of turbo pumps as the capability of the instrument increases from the low-resolution ion trap or quadrupole to the high-end QTOFs and FTMS. At very low capillary flow rates producing “GC-like” vapor loads, pumping becomes simpler while retaining the ease-of-use associated with today’s practice. If lab-on-a-chip comes to full fruition (which may take some time beyond today’s sample handling/separating art) we may see dramatic improvements.

Garner:The biggest obstacle now is translation - how do we get all of the wonderful technology that's been developed into the hands of the people who really need it, who may not be MS experts?

McGinley:Perhaps an obstacle for additional LC–MS development revolves around that adequacy of current MS instruments in the field and customer’s resistance to purchase new equipment in the current economic climate. MS instrumentation is VERY expensive requiring significant capital funding by companies to purchase new equipment. While new MS instruments have new innovations and are more sensitive than older models, for many applications the existing MS instruments in the field are more than adequate to meet the requirements of a particular method. Thus the existing instrument base may actually inhibit new MS purchases (and thus money spent on instrument R and D) leading to a slowdown in instrument development.

McNally and Taylor:Ease-of-use will become a significantly more important factor in order to increase use and acceptance outside traditional MS markets. Data processing and reporting are also key for specific markets.

What was the biggest accomplishment or news in 2008 for LC–MS? Were there any changes or developments since 2007?

Balogh:The two-part question anticipates the answer somewhat. Commercial evolution does not obey the calendar year and true accomplishments are more often evolutionary. Time-of-flight (TOF) was around for many decades until fast electronics and other advances made it feasible. Surface desorption techniques of various types were resurgent almost 5 years ago and are still being scrutinized. One of the most notable recent events came about as a result of coupling ion mobility with QToF design to develop an increased coverage of complex samples. Perhaps among the many adjunctive developments in 2008 and early 2009 we need to acknowledge: a high-order atmospheric GC interface which can be plugged directly into an LC source with no loss of fidelity and; an atmospheric solids analysis probe which emulates ionization techniques such as APCI simply by plugging a sample into the end of a capillary and placing it in a hot nitrogen gas stream in the source again reminiscent of Horning’s work in the 1970s.

McGinley:While not noticed by most, one piece of news for 2008 that was highlighted at the Beijing Olympics was the success of LC–MS techniques in identifying drug doping. Several notable athletes tested positive for performance-enhancing drugs and many others withdrew from participating in the Olympics to avoid drug testing. This really highlights the success of drug testing programs that use advanced analytical technologies like LC–MS. Doping athletes now realize that they cannot beat the system and this new culture of “fairness” would not have been possible without advances in LC–MS instruments. Most LC–MS drug-testing methods are highly sensitive and rugged such that they cannot be “fooled” by the various masking techniques that doping athletes performed in the past.

McNally and Taylor:The biggest accomplishment for LC–MS in 2008 was the sensitivity improvements in triple quad technology and the introduction of a bench top Orbitrap capable of giving ultra-high resolution.

If you are interested in participating in any upcoming Technology Forums please contact Assistant Editor Meg Evans for more information.