Tandem Mass Spectrometry in the Clinical Lab

Tandem mass spectrometry (MS/MS) is a methodology with so much versatility that new usages and applications seem to arise daily. MS/MS began as strictly a research tool, but over the last 20+ years it has made its way firmly into the clinical laboratory. The basic start of that transition came roughly 20 years ago when MS/MS assays were developed that allowed multiple intermediates of metabolism to be identified and quantified using a single punch from a dried blood spot. That development with this technology revolutionized newborn screening in the US over the next decade. Since then, more and more clinical uses for MS/MS have been recognized and developed.

Watching the growth of clinical MS/MS assays in hospital labs has been fascinating. As a reflection of this clinical emergence, journal articles containing MS/MS have increased in number over the same time period. For example, in 1998 the first MS/MS article appeared in the journal, Clinical Biochemistry. Between 1998 and 2003, 0 – 2 MS/MS articles were published each year, but from 2004-2007 that number was in the teens. From 2008-2010 more than 25 articles each year contained MS/MS technology, and from 2011 – 2013 that number ranged from 35-55 MS/MS-containing articles per year.

Initially, clinical applications using MS/MS were for limited assays, including newborn screening, confirmatory testing for inborn errors of metabolism (IEM), and for specific drugs, especially the immunosuppressant drugs. Testing quickly grew beyond drugs and toxicology using MS/MS methods, as the versatility of this testing became apparent. Assays began appearing for accurate measurement of Vitamin D, thyroid hormones and steroid hormones, to name only a few. In addition most MS/MS methods are sensitive enough that sample volumes requirements are small, or the assay can be performed using dried blood spots. Also, the ability to multiplex and measure multiple analytes in a single sample added to the utility of this methodology. Examples include 5 steroid hormones, 30+ analytes for IEM diagnosis or 200+ analytes for toxicology screening, all of which can be analyzed in a single sample within a short period of time.

As common as MS/MS assays now are in clinical laboratories, like early PCR technology, they have remained mostly manual tests run in specialized sections of the lab. They have required technical expertise and a love of hands-on, manual bench work. That is beginning to change with the advent of MS/MS instruments for bacterial identification and the entrance of MS/MS into the microbiology lab. This was the first MS/MS developed for a single, dedicated purpose and intended to require minimal manual intervention, either with day-to-day operation, or with maintenance and troubleshooting. This development clearly demonstrated that MS/MS can begin to approach the more plug-n-play type of technology needed for more fast-paced clinical labs. Developments like this will allow MS/MS to be integrated into more automated labs and ensures its future in the clinical laboratory.

-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.

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