Once upon a time, certainly far enough back in time to when I was a young trainee, clinical mass spectrometry was regarded as an art form. The whole process carried such an air of mystery that most sensible clinical laboratorians did their best to avoid issues such as the complex, smelly and sometimes downright toxic solvent extraction procedures, manual tuning, manual sample injection and use of an instrument that only operated 10% of the time. So accordingly, the technology was consigned to a few specialist laboratories offering toxicological, metabolite and endocrinology tests that just could not be performed using colorimetric, fluorimetric or immunology approaches that could be adapted to the rapidly evolving clinical analyzers. And there the technology lay for several decades.
Tuning A Mass Spec
And then came along tandem mass spectrometry which has revolutionized the whole concept of clinical mass spectrometry. The original technology of gas-chromatography- mass spectrometry was limiting in its applications to compounds that could first be made volatile and that would separate down a chromatography column, sometimes with a 1 hour or longer separation time. Tandem mass spectrometry with or without prior HPLC or fast LC separation has the advantage of being able to analyze non-volatile compounds and in some instances does not even require smelly solvent extractions or prior separation on a column( a process known as flow injection, not LC-MS/MS as many publications describe). The technology has been successfully applied to the measurement of a wide range of biomarkers. Initial applications were in the fields of toxicology, endocrinology and metabolic testing but the technology can easily be used for many more of what are regarded as routine clinical chemistry tests. Enzymes such as AST and ALT can be measured by monitoring the production of amino acid products in an in vitro rate reaction system. Not only could we directly measure uric acid but we could include a whole host of other pyrimidines and purines at the same time so that a diagnosis of xanthinuria will no longer be missed. Creatinine, one of the first biomarkers ever measured in the clinical lab, but blighted with interferences using picric acid based chemistry, can be routinely accurately measured using an appropriate isotope-labeled internal standard. Using multiple reaction monitoring (MRM) approaches, many of these analytes could be measured simultaneously, reducing the need for multiple platforms.
It’s still a long shot to imagine all labs utilizing the technology but the rapid uptake of tandem mass spectrometry and the very clear interest in our profession based upon the numbers of methods papers in journals such as Clinical Chemistry, and growth of training webinars and other courses makes me think that this it is a reality that we will see this technology in all labs one day. And all mass spectrometers today tune automatically, and with appropriate maintenance most of them function all of the time. A couple of years ago, a dear friend and colleague of mine asked me to give rounds at his institution and specified that I shouldn’t talk about tandem mass spectrometry on this occasion, which I somehow managed to do, however painful. About a year later, I received a phone call from the colleague saying, maybe a little tongue in cheek, “Guess where I am?” He was visiting one of the manufacturers about to purchase at least two tandem MS systems. My response Q.E.D! How about yourself, the reader? Have you made the change up yet and does it work for you?