Biomedical Engineering Reference
In-Depth Information
Pitfalls of LC-MS/MS in the Clinical Laboratory
Christoph Seger and Michael Vogeser
Abstract
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 immunoas-
says. 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,
C. Seger , Ph.D. (
*
)
Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL),
University Hospital Innsbruck , Innsbruck , Austria
e-mail: Christoph.Seger@uki.at
M. Vogeser , M.D. (
*
)
Institute of Clinical Chemistry, Hospital of the University of Munich , Munich , Germany
e-mail: Michael.Vogeser@med.uni-muenchen.de
