Pitfalls of LC-MS/MS in the Clinical Laboratory

  • Christoph SegerEmail author
  • Michael VogeserEmail author


The technical maturation of liquid chromatography tandem mass ­spectrometry (LC-MS/MS) hyphenations brought this technology into most of the major clinical laboratories worldwide. It found its sound place amongst major basic routine technologies of laboratory medicine as enzyme based assays or immunoassays. LC-MS/MS extended the technological armamentarium of clinical laboratories significantly, both in analytical and economical terms. Especially in therapeutic drug monitoring, endocrinology, and toxicology, it became an indispensable routine tool.

Although well designed LC-MS/MS assays generally outperform immunoassays due to their accuracy, sensitivity, precision, and inherent multiplexing capability, they are not free from analytical problems. Besides limitations in selectivity—isobaric analytes cannot be distinguished—sudden and unpredictable ion yield attenuations, often known as “ion suppression effect,” have to be considered the Achilles heel of quantitative bio-analytical mass spectrometry. Ion yield attenuation is compromising both the accuracy of an assay and its precision. It can easily lead to gross errors in analyte quantification.

Co-medications or constituents found in pathologically altered patient specimen are major causes for both ion yield fluctuations. Special measures have to be taken to reduce such effect and cause has to be taken to evaluate these accuracy limiting interferences prior to bringing an LC-MS/MS assay into the highly regulated clinical routine environment.

Lacking assay accuracy may also stem from the fact, that most LC-MS/MS methods used in clinical laboratories are still locally designed laboratory-developed tests operating on very heterogeneous instrument configurations. Consequently, assay heterogeneity and lacking traceability to reference procedures or materials leads to an increased imprecision in proficiency testing as well as to inaccurate result reporting if basic rules of assay validation and “post marketing” surveillance are violated.

The position of LC-MS/MS and its advantages / disadvantages compared to immunoassays will be discussed. Technical limitations and analytical problems of LC-MS/MS instrumentation will be critically evaluated in the light of technical development.


Matrix Effect Therapeutic Drug Monitoring Proficiency Testing Target Analyte Atmospheric Pressure Chemical Ionization 
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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL)University Hospital InnsbruckInnsbruckAustria
  2. 2.Institute of Clinical ChemistryHospital of the University of MunichMunichGermany

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