During the past 15 years, liquid chromatography tandem mass spectrometry (LC-MS/MS) has evolved into a vital technology used to perform routine tests in many clinical laboratories, writes Paul J. Jannetto, PhD, DABCC, FACB, MT (ASCP), in the July issue of CLN.

Historically, LC-MS/MS had been used primarily by research, pharmaceutical, or commercial laboratories; however, advances in the technology, decreasing costs for basic systems, intelligible software, an increased number of published protocols and methods, and the release of Food and Drug Administration-approved kits has enabled more clinical laboratories to pursue these instruments as viable clinical analyzers, according to Jannetto, a senior associate consultant at the Mayo Clinic in Rochester, Minnesota.

LC-MS/MS is a powerful qualitative and quantitative analytical technique with a wide range of clinical applications, including therapeutic drug monitoring, toxicology, endocrinology, pediatrics, microbiology, and the emerging field of proteomics. Interest in the clinical utility of mass spectrometry continues to grow, evidenced by the ever-growing number of LC-MS/MS publications and conferences, as well as the recent launch of AACC’s Mass Spectrometry and Separation Sciences Division.

Recognizing LC-MS/MS as a strategic technology, many clinical laboratories are now using this technology in lieu of other methodologies. It gives clinical laboratories the ability to multiplex, identifying and quantifying several analytes of interest simultaneously. Multiplexing lowers the cost per test.

Today, it is the leading technology used in pediatric laboratories for newborn screening programs due to its versatility, sensitivity, and specificity. For example, it is used for the measurement of acylcarnitines for medium chain acyl coA dehydrogenase deficiency and other amino acid disorders like phenylketonuria.

Other benefits of LC-MS/MS include extended measuring ranges and the ability to measure multiple steroids at once, known as complete steroid profiles, compared with measuring individual steroids in separate immunoassays.

Another expanding area for LC-MS/MS is in the field of proteomics. While MS/MS typically has limits to the size of molecules it can measure (i.e. m/z 2,000), larger proteins or peptides can be digested prior to measurement. Immunoglobulins represent one class of compounds with molecular weights >150 kDa that need to be digested before LC-MS/MS analysis. However, they are key biomarkers for immunity, autoimmunity, cancer detection, and immune system function.

While LC-MS/MS is already a mainstay in several areas of the clinical lab, new applications in metabolomics and metallomics are being investigated. Furthermore, some institutions already are using MS/MS outside of the clinical laboratory.

The technology is not without challenges. As a high-complexity system, LC-MS/MS requires a high level of technical expertise to develop and validate lab-developed tests as well as troubleshoot the instruments.

Pick up the July issue of CLN and read more about the versatility of LC-MS/MS and its strengths and limitations.