Biomedical Engineering Reference
In-Depth Information
For instance, if comparing sirolimus assays it is striking that the CV of the
LC-MS group is clearly above that of the sirolimus-CMIA group. An additional
assay imprecision of approximately 7 % can be observed. It is independent from the
analyte concentration; hence it does not represent a loss of assay sensitivity at a
lowered analyte concentration, but an additional contribution to the measurement
uncertainty, which only manifests itself in the total picture of the inter-laboratory
test. The causes for this are unclear. However, one may speculate that, especially in
the area of sirolimus TDM, where for several of the past years many of the labora-
tories have used chromatographic methods for lack of alternatives [
70
] , outdated
technologies (e.g. LC-MS instead of LC-MS/MS) and heterogeneous (in-house)
calibration systems (single point vs. multipoint calibrations, different internal stan-
dards, etc.) are being used. Here, the medium-term goal of LC-MS/MS platform
development must be an improvement of the inter-laboratory PT CV to <10 % in the
therapeutic range.
4
Outlook/Conclusion
In summary LC-MS/MS has doubtlessly a high inherent potential for selectivity and
accuracy. However, application of this technology is not automatically or necessar-
ily translated into accurate results. Its pitfalls have to be recognized and must be
addressed systematically. In particular interferences from in-source transformation
of metabolites, differential matrix effects of analyte and internal standard and
isobaric transitions can lead to inaccurate results of LC-MS/MS analyses. Further
technological developments will probably help to make LC-MS/MS assays more
robust towards such interferences, but clinical chemists have to remain watchful for
inaccuracies also with powerful and fascinating technologies
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