I am amazed by how often I hear someone say that mass spectrometry doesn't need chromatography. Each year I attend a number of conferences, and some are predominantly focused on mass spectrometry, whereas others are more focused on chromatography. I have mentioned before that I feel I need a reversible t-shirt that says, "I am a chromatographer" on one side and "I am a mass spectrometrist" on the other. Maybe it needs to be a polo shirt to be more appropriate for conference wear, but having this would allow me to better blend in with the extremists from each side. To the extremist chromatographer, the mass spectrometer is just a fancy detector. To the extremist mass spectrometrist, the chromatograph is simply an inlet. In fact, I have heard one prominent analytical chemist remark, "if it can't be done with mass spectrometry, then it's probably not worth doing!" Much the same could be said regarding chromatography, given its widespread use throughout myriad science and engineering fields.
I was raised as a chromatographer, but nearly all of our work also involves mass spectrometry of some variety. It is hard to imagine an optimum work-flow for analysis of a trace compound in a complex matrix that does not involve both chromatography and mass spectrometry. Without a detector capable of providing sensitive qualitative information, chromatography has to rely simply on retention time matching to verify the identity of a chemical compound observed in a chromatogram. Without a means to reduce the complexity of a dirty sample, mass spectrometry (in most embodiments) is subject to significant matrix effects, which hamper sensitivity and reproducibility. Even so, there are recent developments on both sides that might reduce the co-dependence of the two techniques.
For the past ten years, ambient ionization (AI) techniques have been introduced. These include desorption electrospray ionization (DESI) and direct analysis in real time (DART), among many, many others that also clearly challenge the availability of unused acronyms in the scientific literature! A few defining features of AI include ion generation under ambient conditions, the ability to independently optimize sample introduction and ionization variables, and the reduction of matrix effects relative to traditional atmospheric pressure ionization techniques (i.e., electrospray ionization and atmospheric pressure chemical ionization). A wide variety of hardware orientations and modes of ionization are available to address different analytical problems and sample types. Several configurations have been commercialized. So, if you want to do mass spectrometry without chromatography, it will be necessary to use a technique, such as ambient ionization, that can ameliorate matrix effect issues. Your biggest challenge might be picking which one to try.
Some might say that traditional chromatography is not needed, since we can also do gas phase separations of ions using ion mobility spectrometry (IMS). Though originally conceived and used many years ago, IMS has recently experienced a heavy resurgence, primarily driven (I think) by the availability of high end commercial systems that incorporate the technology. IMS involves the drift of ions through a tube against a carrier buffer gas. It has many advantages including the ability to separate conformers of ions (because size, charge, and shape affect mobility) and separations are accomplished in the millisecond regime. Thus, IMS has enjoyed significant use placed between chromatographic separations (seconds to minutes) and time of flight mass spectrometry (microsecond timescale). IMS adds a different dimension of separations, and you will often see mobilitygrams displayed with mass-to-charge ratio on the x-axis and ion mobility on the y-axis. They look a lot like represented chromatograms from two dimensional separations (but those have time on both axes). While IMS does provide enhanced means for gas phase speciation, it still relies on the efficient generation of ions. Thus, to do that well, you better have chosen your appropriate AI technique, done extensive sample preparation, or have a chromatography front end to segregate your sample, so you don't get killed by matrix effects.
What about doing chromatography without mass spectrometry detection? Here I think there are currently less choices. Even in a court of law, to prove that a compound is what you say it is, there should be three characteristic ions given. To do this by orthogonal chromatography and retention time matching would be harder to defend. If you look at other detectors, most of the widely used ones are based on standard spectroscopy. In the liquid phase, limited information can be obtained from a UV/Vis detector, except maybe to associate the broadband absorption spectrum with a class of compounds. In the gas phase, absorption spectroscopy has not been popular, but that might all be about to change. We have been working with a company to help develop a vacuum ultraviolet (VUV) absorption detector for gas chromatography that has recently been released onto the market. Our first paper on the subject has been submitted, and we have presented the results at conferences. In short, all chemical compounds absorb in the VUV range (the detector actually measures broadband absorption from 120 – 240 nm), and in the gas phase, they all have a unique absorption spectra. So, we believe that this will be a new means to obtain sensitive qualitative information without the need for mass spectrometry. I'll be writing much more about VUV detection in the future.
Getting back to the question at hand, does mass spectrometry need chromatography? I think that the answer is yes – in most cases where highly sensitive detection is needed in the presence of a complex sample matrix, the co-dependence of these techniques is currently a necessity. But, I guess it is good that the extremists are out there who believe otherwise. They will continue to drive research toward new and improved means for analysis, and one day maybe this marriage can be dissolved. Until then, I think our group will largely remain working with one eye on optimizing each side of the union. We'll just turn our shirts inside out depending on with who m we need to fit in.
Kevin A. Schug, Ph.D.
Shimadzu Distinguished Professor of Analytical Chemistry
Department of Chemistry & Biochemistry
The University of Texas at Arlington
Arlington, TX USA