Biomedical Engineering Reference
In-Depth Information
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.
1
Introduction
Laboratory investigations play an essential role in medicine. Laboratory results are
taken into consideration in about two thirds of all medical decisions in medical
systems of industrialized countries today. The vast majority of clinical chemistry
analyses are based on few analytical principles including photometry, ligand bind-
ing assays and potentiometry. For these standard methods complete automation has
been achieved and multi-channel, random access analyzers realize several hundred
analyses per instrument and hour on a very high level of user-friendliness. Conse-
quently, clinical chemistry is very cost efficient today; typically clinical chemistry
analyses contribute less than 5 % of all costs of tertiary care hospitals.
The development of photometric and ligand-binding based analytical methods in
clinical chemistry between the 1960s and the 1990s has dramatically changed many
fields in medicine and substantially enhanced the diagnostic potentials in patients'
care globally. However, it must be recognized that these standard techniques still are
compromised by important shortcomings: For many analytes cross-reaction with
similar, naturally occurring or xenobiotic compounds or the impact of unspecified
matrix compounds on signal generation limits the reliability of results, e.g. in the
quantification of steroid hormones. Since the specificity of such tests often differs
between different assays, method specific reference ranges must be interpreted in
clinical decision making today. Although by principle extremely versatile, the
development of new ligand binding tests in an industrial dimension is very expen-
sive, resulting in the lack of routine methods for many desirable analytes, in particu-
lar for drug testing in therapeutic drug monitoring. Many small molecules can
neither be addressed by photometric tests nor by ligand binding methods due to
their particular molecular structure (e.g. methylmalonic acid). Current standard
methods may be implemented on a multi-channel analyzer but are by principle sin-
gle-target analyses which are not primarily reading out analyte profiles.
Mass spectrometric methods have a huge potential to overcome these limitations.
While GC-MS has found a fundamental role in toxicology and occupational medi-
cine it did not find a place in the routine clinical chemistry laboratory due to its very
demanding handling not suitable for a 24 h/7 day service laboratory setup. The
introduction of LC-MS has improved the practicability and robustness of highly
specific and highly multiplexed mass spectrometric analyses very substantially.
