It’s a great time to be analytical scientist. Technology in this field is developing rapidly, with ever-increasing capabilities. However, the increasing reliance on mass spectrometry (MS) that I see, especially amongst young scientists, makes me uneasy. Is MS becoming so dominant that people forget that there are other ways of analyzing things? Already, some people in my own field of metabonomics are reluctant to move outside the confines of mass spectrometry. There is an attitude that if it can’t be done by LC-MS, then it can’t be done at all. Of course, that is simply untrue. There are many answers beyond LC-MS, but you have to be willing to try a different (and possibly less sexy) approach.
I am by no means suggesting that we go back to the past (though I do have a museum of old analytical equipment, if you’re interested). But consider that, in the space of 30 years, mass spectrometry has progressed from a specialist instrument requiring intensive training and lengthy analysis, to something that any competent analytical chemist can use. When I did my first mass spectrometric analyses, it took a whole day to analyze a single spectrum (printed on photosensitive paper – we counted the mass units by hand!) The power and ease of today’s mass spectrometers is wonderful by comparison. So yes, it would be ridiculous to turn our backs on the wonderful power and ease of use of modern mass spectrometry. But... we must also be aware of its limitations, and keep an open mind to alternatives. If our starting point is always to assume that we will analyze the sample by LC-MS, we can forget to ask the most important question – what are we trying to learn from our analysis? MS is remarkably sensitive (though this is structure dependent). But if you find that you have to dilute a urine sample 10,000 times to get the analytes you want to measure into the linear range of the instrument, it’s time to ask yourself if your approach is the best one. If all you want to do is quantify a particular molecule, why not use something like LC-UV? Since the 1970s, and assuming a suitable chromophore, we’ve been analyzing samples with LC-UV at 1 ng/mL with great selectivity, precision and accuracy. Plus, for the cost of one LC-MS system, you could buy ten LC-UV systems.
I work with colleagues at Imperial College who use both 1H NMR spectroscopy and LC-MS for both small and large-scale metabonomic analyses. At first sight the use of NMR spectroscopy and LC-MS for the same analysis seems a bit strange, as it is a common perception that the former is rather insensitive - so how could it compete with MS? However, in my experience, the combination of the two is brilliant. They are quite orthogonal in the metabolites they access, and the information provided is complementary. In addition 1H NMR spectroscopy is inherently quantitative, wonderfully reproducible, contains a lot of structural information and is not subject to ion suppression! Add in LC-MS and you have a very powerful combination for the analysis of complex mixtures such as biofluids. No doubt, over time, pragmatism will prevail and techniques currently out of favor will find their place again. And perhaps in a few years, a new technique may even come along to steal mass spectrometry’s crown and shake us all up again. It’s one of the things I love about analytical chemistry. All I ask is that while we welcome the latest and greatest, let’s not lose our perspective and forget the old favorites.
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