Biomedical Engineering Reference
In-Depth Information
Fouling or Malfunction of Mass Spectrometer
During routine use, a mass spectrometer might get dirty or contaminated, such as the
coronal needle, orifice, or rods of a quadrupole, particularly when extracted samples
are not clean enough, such as those by protein precipitation. When this happens, the
IS response will normally decrease. Sometimes, the signal might be completely lost,
e.g., blockage of the orifice. A special phenomenon with the commonly used triple
quadrupole MS is so-called “charging,” where IS responses decrease sharply at the
beginning of a batch and then decrease more and more slowly, quite similar to the
current vs. time curve during the charging of an electric capacitor (Fig.
10
).
However, a contaminated mass spectrometer may cause various response trends toward
different compounds. For example, after a triple quadrupole MS was contaminated with
ascorbic acid, different response patterns were observed for levothyroxine (ANA), liothy-
ronine (ANB), and their internal standard (thyroxine-
13
C
6
) during the repetitive injections
of pure reference solutions containing these three components (Fig.
11
). The responses
of ANA were relatively stable while those of ANB and IS decreased significantly over a
time period of about 1 and half hours, which resulted in increasing analyte/IS response
ratios for levothyroxine and decreasing ratios for liothyronine.
To solve these problems, the contaminated components in the mass spectrometer
should be cleaned. Moreover, postcolumn switching or splitting should be consid-
ered to prevent or reduce the occurrence of contamination as well as to improve
signal stability [
39
] .
Ion Suppression or Enhancement
Ion suppression or enhancement (matrix effect) by coeluting components including those
from previous injections (late-eluting components) is a common phenomenon in LC-MS
and it can seriously degrade the accuracy of analytical results if it is not appropriately cor-
rected by the use of internal standards. Although it is more common with electrospray
ionization (ESI), it can also exist to a less degree with APCI (atmospheric pressure chemi-
cal ionization). The compounds that cause ion suppression or enhancement are usually
from coextracted matrix components, but they could also come from other sources, such
as remaining salt residues from sample clean-up, additives in a mobile phase, Li-heparin
anticoagulant, and polymers contained in storage devices [
13,
34,
40
] .
To reduce matrix effect, it is important to obtain cleaner extract and use adequate
separation. In the presence of late-eluting components that cause matrix effect,
adjustment of retention time, run injection cycle time, and/or postinjection column
washing should be used to eliminate or reduce their impact.
Inter Matrix Lot or Inter Sample Differences
Despite the wide application of matrix-matched calibration, it is very difficult or
even impossible to completely match the matrix of every sample due to diversities
of subjects, particularly human subjects, and the dynamic nature of in vivo metabolism.
