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RAPID COMMUNICATIONS IN MASS SPECTROMETRY
Rapid Commun. Mass Spectrom. 2006; 20: 2419–2426
) DOI: 10.1002/rcm.2611
Published online in Wiley InterScience (www.interscience.wiley.comSystematic examination of the signal area precision
of a single quadrupole enhanced low mass option
(ELMO) TSQTM mass spectrometer
Klaus Fischer*, Susanne Hoffler and Axel MeyerUniversity of Trier, Faculty VI – Geography and Geosciences, Department of Analytical and Ecological Chemistry,
Behringstr. 21, 54296 Trier, Germany
Received 7 April 2006; Revised 7 June 2006; Accepted 14 June 2006
*CorrespoGeographcal ChemE-mail: fi
To examine the precision of the signal area response of an enhanced lowmass option (ELMO)MSQTM
mass spectrometer, operated in the negative electrospray ionization (ESI) mode, extended tests were
performed, using flow injection analysis mass spectrometry (FIA-MS). Analytes were nitrate, nitrite,
malonic acid, and D,L-mandelic acid. Composition and concentration of injected samples, application of
an ASRS anion suppressor and of the cone wash unit, methanol addition to the FIA flowmedium, and
the voltage bias of the hexapole transfer lenswere test variables. Individual test cycles comprised up to
90 injections, processed within 20h. With a few exceptions the signal response tended to decline over
time leading to a loss of more than 80% of the initial signal area in extreme cases. A hexapole radio-
frequency (RF) voltage bias of S0.3V led to an overall low detector response and to high losses of
sensitivity over time. Other correlations between the insufficient signal reproducibility and FIA-MS
operating conditions could not be established. The test scheme gave hints how to localize the cause of
the mass spectrometer malfunction. The repetition of the test scheme after remedying the detected
electronic default demonstrated that relative standard deviations less than 5% can be achieved for a
sequence of 30 injections if methanol is added to the FIA flow medium and if a suppressor is used.
Based on these findings a recommendation is formulated to supplement current test schemes for
instrument performance verification by a detector response precision criterion. Copyright # 2006
John Wiley & Sons, Ltd.
Ion chromatography/mass spectrometry (IC/MS) parallels
in most of its technical design high-performance liquid
chromatography/mass spectrometry (HPLC/MS) but,
depending on the manufacturer, there are some specific
features owing to the fact that the mass spectrometer has to
cope with common aqueous IC eluents, containing less
volatile acids, bases, buffers, or ion-pairing reagents. For the
analysis of small inorganic ions or low molecular weight
organic compounds, high detection sensitivity in the low
mass range is required and this is usually not offered by
standard single quadrupole MS systems. For instance, the
Finnigan enhanced low mass option (ELMO) MSQTM
detector (Thermo Electron Corp., Waltham, MA, USA),
which is coupled with an IC unit by Dionex Corp.
(Sunnyvale, CA, USA) to design a completely configured
IC/MS system, is equipped with a cone wash device and
with an ELMO detector, comprising a 5-mm hexapole radio-
frequency (RF) transfer lens and a separate RF generator.
Currently, themain classes of organic compounds targeted
by single quadrupole IC/MS are low molecular weight
organic acids,1–5 carbohydrates,6,7 and synthetic chelating
agents.8–10 Important inorganic analytes are oxyhalogenides,
ndence to: K. Fischer, University of Trier, Faculty VI –y/Geosciences, Department of Analytical and Ecologi-istry, Behringstr. 21, 54296 Trier, Germany.scherk@uni-trier.de
e.g. perchlorate, bromate, and iodate,4,11–16 and simple
halogenides, e.g. iodide.17,18
In view of the wide use of single quadrupole mass
spectrometers as mass-selective detectors, such instruments
should be suited for the quantitative analysis of large sample
series on a routine level. In addition to other analytical
quality parameters, repeatability, reproducibility and robust-
ness are decisive performance criteria.
From the beginning of our systematic performance tests of
a newly installed IC/API-MS system operated in the
negative electrospray ionization (ESI) mode we were
confronted with an insufficient repeatability of quantitative
results and with a serious signal drift, mainly in the form of
losing sensitivity over time. To document the state of the
mass spectrometer and to uncover the cause of its
malfunction, extended repeatability and reproducibility tests
were performed, varying the relevant operation parameters.
The test results should enable us to decide whether the
problem is caused by inadequate operation or by instru-
mental shortcomings. Furthermore, the test scheme should
offer the versatility to be useable for the performance control
of different MS systems and it should be capable of
Copyright # 2006 John Wiley & Sons, Ltd.
2420 K. Fischer, S. Hoffler and A. Meyer
scrutinizing the effectiveness of technical modifications
under realistic analytical conditions. Conducting the test
schedule over more than half a year, several thousand pieces
of data were gathered.
The test scheme helped to identify the cause of the
malfunction of the MS device. After technically upgrading
the detector, which should solve the electronic problem, some
of the test series were repeated. The presentation of the most
important test results, characterizing the situation before and
after the technical upgrade, has the following aims:
(a) t
Cop
o share the gained practical experience and to assist
other users facing similar problems in trouble shooting;
(b) t
o show which of the tested methodological and instru-mental parameters had a systematic effect on the detector
performance;
(c) t
o provide reference data on analytical repeatability andreproducibility, achievable with an ELMO TSQTM detec-
tor in the negative ion mode under realistic conditions;
(d) t
o generate discussion on how to assess system perform-ance data and how to define whether the instrumental
performance is in a ’normal’, acceptable range or not; and
(e) t
o initiate considerations concerning an extension of man-ufacturers’ responsibility for product quality, i.e. integ-
ration of standardized reproducibility measurements in
mass spectrometer functional verification protocols.
EXPERIMENTAL
Materials and reagentsAll reagents and solvents were of analytical-reagent grade.
Water was purified by reverse osmosis and then passed
through a Membrapure unit (Astacus Analytical, Boden-
heim, Germany). The purified water was used as flow
medium for the flow injection analysis (FIA)-MS system.
The selected test compounds were: D,L-mandelic acid
(1-hydroxy-1-phenylacetic acid) (>99%; Merck, Darmstadt,
Germany), malonic acid (>99%; Fluka, Buchs, Switzerland),
and standard solutions of nitrate (1 g�L�1; Merck) and
nitrite (1 g�L�1; Merck), prepared from their sodium salts.
Several tests were performed with admixtures of methanol
(for liquid chromatography; Merck) to the flow medium.
InstrumentalThe experiments were designed as flow injection/ESI-MS
analysis. A continuous flow of water or of water/methanol
(3:1, v/v) mixtures was maintained bymeans of a Dionex GP
50 gradient pump. Flow rates between 0.15 and
0.38mL�min�1 were tested but the usual settings were 0.2
or 0.38mL�min�1. The aqueous samples were injected into
the flowmedium (injection volume: 10mL) with a Dionex AS
50 autosampler. The analyte concentrations weremainly 10.0
or 3.0mg�L�1, but several tests were run with concentrations
of 20.0 or 0.1mg�L�1. Two types of samples were measured:
mixtures of two or of all four compounds, equally
concentrated (’multiple component standard’), and single
compound standard solutions. To control the stability of the
samples, a Dionex CD 25 conductivity detector was coupled
in-line before the ESI inlet during several test series.
yright # 2006 John Wiley & Sons, Ltd.
Additionally, a 2mm ASRS-Ultra suppressor (Dionex),
operated in the external water mode, was inserted before
the conductivity cell at specific test subsets. By using two
appropriate PEEK capillaries (length: 20 ft; diameter: 0.005 and
0.01 inch), a back pressure of at least 1250 psi was maintained.
A Finnigan Surveyor ELMO MSQTM mass spectrometer
with API interface, operated in the negative ESI mode, was
used. System control and data processing were handled by
the Dionex Chromeleon 6.40 software. Nitrogen, supplied by
a nitrogen generator, served as sheath and nebulizing gas,
maintaining a nitrogen pressure of 80 psi. The ESI probe
temperaturewas 4508Cor 5508C, cone voltagewas�50V and
ESI needle voltage was �3.0 kV or �3.5 kV. In several tests a
Dionex AXP-MS pump was used to wash the entrance cone
of the mass spectrometer with water or water/methanol
(3:1, v/v). The flow rate of the washing liquid was
0.04mL�min�1. The analytes were monitored in the se-
lected ion monitoring (SIM) mode observing the following
m/z values: 46 nitrite, 62 nitrate, 103 [M–H]� malonic acid,
and 151 [M–H]� mandelic acid. A full-scan mass spectrum
up to m/z 500 of malonic acid showed no peak from the
malonate dianion, m/z 51. Signals indicating the formation
of sodium malonate ion pairs or of ion clusters were also
not present. Signal areas (counts � min�1) were used as
quantitativemeasure. Themass spanwas 0.5 or 1.0 and dwell
times of 0.25, 0.3 or 0.5 s were selected. Alternatively,
negative ion full-scan mass spectra were recorded over the
range m/z 50–500 at a scan time of 0.5 s. The run time per
injection ranged from 7 to 10min. The initial voltage of the
hexapole RF lens bias was �0.3V. This value was raised to
�0.6V as a result of the related test series and finally adjusted
to �1.0V after the technical upgrade of the detector. During
the last minute of every run, the ESI voltage was converted to
positive polarity to avoid an accumulation of negative
charges in the ion focusing region of the mass spectrometer.
Data treatment
Mean values (x), standard deviations (SD), coefficients of
variation (% RSD) and linear regression functions with
regard to possible correlations between signal areas and MS
run time were calculated for all test sequences. Due to the
time-dependent bias of the data series the reliability of the
corresponding means did not increase with the number of
measurements as is expected where errors are randomly
distributed. Therefore, data were recognized as outliers and
rejected only if they could be traced back to improper
laboratory operations or instrument conditions.
In this paper the term ’repeatability’ applies to test schemes
conducted with replicate injections of one standard solution
exclusively. Otherwise the term ’reproducibility’ is used.
RESULTS AND DISCUSSION
Initial situationThe first test series was conducted with the aim of creating a
data matrix which would offer a first insight into the mass
specrometer detector performance, allowing for a rough
estimation of data trends and effect sizes. Therefore, a four-
compoundmixture containing the analytes in concentrations
Rapid Commun. Mass Spectrom. 2006; 20: 2419–2426
DOI: 10.1002/rcm
Table 1. Repeatability of the mass spectrometer response
(SIM signal area) for four analytes, examined with a suite of
four injection sequences (test series 1)
Analyte
Subset #1–20 Complete series (#1–53)
x %RSD %CiSa x %RSD %CiSa
Nitrite 1975 7.4 þ5.7 1690 18.1 �41.9Nitrate 86839 5.2 �5.8 74616 15.8 �39.6Malonic acid 3438 23.8 �44.1 3987 26.5 þ80.6Mandelic acid 19065 17.6 �31.1 18811 11.8 �8.4
aChange in sensitivity: detector response for the last injection relatedto the first injection (both values derived from the linear regressionfunction).Analyte concentration of the multiple component standard: nitriteand nitrate, 10.0mg�L�1; mandelic acid, 10.5mg�L�1; malonic acid,10.9mg�L�1Total run time 17h; run time for subset #1–20: 3 h 20min.Time interval between every injection sequence 3h.
Table 2. Reproducibility of the nitrate SIM signal with and
without cone wash (test series 2)
Injection sequence
Without cone wash With cone wash
x % RSD %CiSa x %RSD %CiSa
#1–20 (single standard) 723 23.0 þ9.3 1087 13.1 �0#41–65 (mix) 453 25.9 þ24.8 563 17.7 �12.7Total of single injections 710 21.3 �1.9 966 22.5 �40.4Total of mix injections 455 27.3 þ16.8 515 34.7 �43.7Total series 573 32.7 �26.8 723 41.4 �67.4
aChange in sensitivity: detector response for the last injection relatedto the first injection (both values derived from the linear regressionfunction).Nitrate concentration, 0.1mg�L�1For further details, see text.
Table 3. Reproducibility of the mandelic acid SIM signal with
and without cone wash (test series 2)
Injection sequence
Without cone wash With cone wash
x % RSD %CiSa x %RSD %CiSa
#1–20 (single standard) 99.4 11.6 �12.8 147.8 14.3 þ4.8#21–45 (mix) 67.3 16.6 �11.1 89.4 18.7 �33.6Total of single injections 80.9 35.3 �66.7 120.4 35.7 �61.0Total of mix injections 59.1 28.6 �50.0 83.6 22.2 �43.1Total series 69.2 25.3 �71.8 100.6 36.7 �69.9
aChange in sensitivity: detector response for the last injection relatedto the first injection (both values derived from the linear regressionfunction).Mandelic acid concentration, 0.1mg�L�1For further details, see text.
Examination of the signal area precision of an ELMO TSQTM 2421
between 10.0 and 10.9mg�L�1 was injected 53 times. The
series was subdivided into four injection sequences. The first
sequence comprised 20 consecutive injections. Each of the
following three sequences included 11 injections. Between
every sequence a 3-h interval of continuous FIA-MS
operation without sample introduction was inserted. The
total run time was 17 h.
For the first injection sequence, the relative standard
deviation (RSD) and the change in the detector response
were relatively small for the inorganic ions (Table 1). The
variation of the response data was considerably higher for
the organic acids which showed a loss of 30% ormore of their
respective initial signal areas. Simultaneously, the signal of
the conductivity detector remained almost constant. Its RSD
was less than 2.1% without following any trend.
The heterogeneity of the sensitivity trend established for
the whole test series was remarkably higher than for the first
injection sequence. Whereas the detection sensitivity
decreased almost identically for the inorganic ions by
approximately 40%, it remained nearly constant formandelic
acid and increased by 80% for malonic acid. The divergence
of the sensitivity trends makes it clear that the observed
variations in the mass spectrometer performance cannot be
explained by a simple drift or saturation effect.
Also to be considered are the reasons for the tremendous
differences in the analyte specific detection sensitivities, most
pronounced in the case of nitrite and nitrate. Calculated on
the basis of the response means obtained from the first
injection sequence and taking account of the different masses
of the ions, the detection sensitivity for nitrate is 59 times that
for nitrite. Although the absolute number is not significant,
the order of magnitude was reproduced by many compara-
tive measurements. One reason for the low detection
sensitivity for the nitrite ion might be its tendency to
disproportionate into nitrogen oxide and nitric acid under
acidic conditions (transformation of the nitrite ion into
nitrous acid). This disproportionation is favored by increases
in temperature and of the nitrite ion concentration – both
processes accompany the electrospray formation. Indeed
full-scan measurements of the nitrite standard solutions
showed that small nitrate signals were always present in the
mass spectrum.
Copyright # 2006 John Wiley & Sons, Ltd.
The following measurements (test series 2) were intended
to ascertain the influence of the cone wash device on data
precision. Trends in the detector response should be
compared for single substance and mix injection of nitrate
and mandelic acid. The analyte concentrations were reduced
to 0.1mg�L�1. The single compound standards were injected
30 times, forming three sequences, comprising 20 and 5
injections. Arranged into three intervals, comprising 25 and 5
injections, 35 measurements were made from the multiple
component standard. The whole experiment was performed
twice, first without cone wash, afterwards with such a wash.
Some general trends can be extracted from the test series
(Tables 2 and 3). First, the detector response for the single
compound standard was higher than for the mixed one. For
instance, the mean detector response for nitrate, injected
together with mandelic acid, was 53% of the value
established for the pure nitrate standard, measured at active
conewash (Table 2). Secondly, the operation of the conewash
elevated the detection sensitivity by 10% to 50% but exerted
no clear effect on data variation.
The complete mandelic acid data set is illustrated in Fig. 1.
Despite the high short-time variation of the data, the general
trend is apparent.
A significant time trend of the mass spectrometer signal
was observed while working with smaller injection
sequences (test series 3). After 20 injections of each of the
four single component standards the loss of sensitivity
Rapid Commun. Mass Spectrom. 2006; 20: 2419–2426
DOI: 10.1002/rcm
Figure 1. Repeatability of the mandelic acid SIM response with and without cone wash (test series 2).
The total series comprised 65 injections (30 injections of the single (s) component standard,
35 injections of the multiple (m) component standard). Mandelic acid concentration 0.1 mg�L�1.
Table 4. Repeatability of the SIM signal area for four ana-
lytes, injected with single and multiple component standards.
Situation before MS upgrade (test series 3)
Analyte
Single componentstandard (20 injections)
Multiple componentstandard (25 injections)
x %RSD %CiSa x %RSD %CiSa
Nitrite 9203 6.5 �9.3 2106 6.3 �14.4Nitrate 85908 8.5 �20.7 72551 6.3 �15.5Malonic acid 2151 14.2 �19.1 1035 27.6 �55.6Mandelic acid 27854 6.0 �12.9 13463 12.4 �30.5
aChange in sensitivity: detector response for the last injection relatedto the first injection (both values derived from the linear regressionfunction).Analyte concentrations: nitrite and nitrate, 10.0mg�L�1; mandelicacid, 10.5mg�L�1; malonic acid, 10.9mg�L�1. Run times: Everysequence of 20 injections: 3 h, the sequence of 25 injections: 3 h45min.
2422 K. Fischer, S. Hoffler and A. Meyer
varied between 9.3 and 20.7% (Table 4). The run time per
standard solution was 3 h. The 25-fold injection of the four-
component standard resulted in a considerably higher
depression of the mass spectrometer response for the
organic acids. The %RSD values and the signal area
decrease of the organic analytes correspond very well with
the results of the analogously configured subset #1–20, test
series 1 (Table 1). Paralleling the results noticed with test
series 2, the jointly injected analytes gave a lower detector
response than the individually added ones. This difference
was highest for nitrite which can be interpreted as an
additional indication of the occurrence of nitrite-degrading
reactions.
To optimize spray formation and to enhance the ion
transfer efficiency, organic modifiers, e.g. methanol, iso-
propanol or acetonitrile, are often added to aqueous eluents
before they enter the ESI interface. To reduce the salt content
of typical IC eluents and to minimize ion pair formation and
ion clustering in the atmospheric pressure region, a
Copyright # 2006 John Wiley & Sons, Ltd.
suppressor, functioning as an ion exchanger, is coupled
between the column and the mass spectrometer interface.
The influence of such analytical conditions on detection
sensitivity was checked with a set of four test series.
Therefore, a standard solution combining all four com-
pounds in concentrations of 3.0mg�L�1 was used. For each
test series 30 injections of the multiple component standard
were made within 8 h. Equally concentrated solutions of
nitrate and ofmandelic acidwere also analyzedwithin a total
run time of 10 h.
The results for nitrite and mandelic acid are depicted in
Figs. 2(A) (nitrite) and 2(B) (mandelic acid), respectively. The
loss of sensitivity spanned from 65.1% (test series without
methanol addition/without suppressor) to 50.5% (with
methanol/without suppressor). The highest initial detection
sensitivity for nitrite was achieved working without altera-
tion of the initial FIA-MS conditions. The in-line coupling of
the suppressor together with addition of methanol severely
depressed the nitrite signal. On several occasions the nitrite
signal was not discernible from the baseline noise, making
the determination of the signal repeatability impossible
under that condition. This finding, which is confirmed later
by measurements with the upgraded MS system, supports
the hypothesis that the low signal response for nitrite follows
from its disproportionation, combined with the low dis-
sociation degree of the nitrous acid at acidic pH. The
suppressor promotes this reaction by converting sodium
nitrite into nitrous acid. Addition of methanol did reduce the
detector response to a certain extent but also led to a more
stable detector response.
In the case of mandelic acid (Fig. 2(B)) the addition of
methanol, at least without suppressor, is advantageous for
maximum detection sensitivity. As with the other tests the
loss of signal intensity over time was high and amounted up
to about 75% of its initial value. In terms of detection
sensitivity, the parameter combination ’without suppressor/
without methanol’ was the least favorable one. When
comparing the two tests with addition of methanol, the
adverse effect of the suppressor operation is hard to explain.
Rapid Commun. Mass Spectrom. 2006; 20: 2419–2426
DOI: 10.1002/rcm
Figure 2. Influence of methanol addition and suppressor operation on MS sensitivity and SIM signal
repeatability for nitrite (A) and mandelic acid (B). Multiple component standard (concentration:
3.0 mg�L�1 of each analyte), flow rate 0.2 mL�min�1, water/MeOH (3:1, v/v), Dionex Ultra suppressor,
external water mode.
Examination of the signal area precision of an ELMO TSQTM 2423
Since this compound was already injected in its free acid
form, the suppressor should not exert any influence on the
degree of dissociation of the acid. A certain portion of the
acid molecules might have been transferred from the flow
medium into the suppressor regenerant by penetrating the
suppressor membrane. In contrast to this, the use of the
suppressor (without methanol) was advantageous to achieve
maximum sensitivities for nitrate and malonic acid.
Sequences of individual determinations of mandelic acid
and nitrate were processed after the mix measurements.
Their results are in good qualitative and, in some respects,
even quantitative agreement with former findings, indicat-
ing that they are caused more by systematic than by random
effects or circumstances.
The hexapole RF transfer lens, mounted instead of a
conventional quadrupole-like RF/dc prefilter before the mass
analyzer in the ELMO MSQTM, focuses the ions produced in
the ESI source and transmits them to the quadrupole analyzer.
Increasing the hexapole offset voltage increases the kinetic
energy of the ions and accelerates their transfer into the mass
analyzer. Therefore, the setting of the lens biasmight be crucial
for detection sensitivity generally and for the mass-to-charge
dependence of the MS response especially.
Copyright # 2006 John Wiley & Sons, Ltd.
Indeed the RF voltage bias test demonstrated a consider-
able effect on MS sensitivity and signal repeatability
(Table 5). Except for malonic acid, the highest initial and
mean sensitivity was established with a lens bias of �0.8V.
The loss of sensitivity and the RSDs were lowest at �0.6V.
Under these conditions, between two-thirds and half of the
initial detection sensitivity remained until the last injection.
A second test series with the same lens bias including
60 consecutive injections resulted in a somewhat better
repeatability probably due to the smaller number of
injections. At a lens setting of �0.3V the detector response
declined extremely for all analytes during the measuring
period. For instance, the means (relative peak areas) of #1–3
and of #78–80, malonic acid, were 1706 and 233, respectively.
The decline in the mandelic acid signal was of the same
order of magnitude. The mean values of the first and last
three injectionswere 7174 and 1301, respectively, indicating a
loss of sensitivity of 82% on that calculation basis.
Considering the significant effect of the RF voltage bias on
the detector performance it is obvious that the proper
selection of this parameter helps to mitigate but not to solve
the problem. On the other hand the finding that a certain
correlation between the kinetic energy of the ions and the
Rapid Commun. Mass Spectrom. 2006; 20: 2419–2426
DOI: 10.1002/rcm
Table 5. Influence of the hexapole RF transfer lens voltage bias on SIM signal repeatability
Analyte
RF voltage bias
�0.3V �0.6V �0.8V
x % RSD %CiSa x %RSD %CiSa x %RSD %CiSa
Nitrite 186 61.3 �92.2 337 16.5 �37.3 683 32.3 �59.1Nitrate 8635 52.3 �83.6 12738 14.9 �37.0 20338 30.4 �57.4Malonic acid 513 83.3 �99 4102 19.7 �46.7 2183 41.5 �74.5Mandelic acid 2464 70.6 �97.7 5349 22.1 �50.9 8314 36.9 �54.2
aChange in sensitivity: detector response for the last injection related to the first injection (both values derived from the linear regressionfunction).Eighty injections of the multiple component standard (3.0mg�L�1 of each analyte) per lens voltage. Test period per voltage: 17 h including seven1-h breaks between every sequence of 10 consecutive injections. The FIA-MS system operated continuously without a break.
2424 K. Fischer, S. Hoffler and A. Meyer
drift of the detector response exists could have led to the
hypothesis that the cause of the instrument malfunction
might be localized in the hexapole itself or in the ion transfer
region between the hexapole and the quadrupole analyzer.
This intensive examination enabled experts fromDionex and
Thermo Electron to find that the problems were caused by an
insufficient grounding of a specific component of the
hexapole in close vicinity to the quadrupole analyzer. In
parallel with the accumulation of negative charges at this
point, repulsive electrostatic forces were exerted on nega-
tively charged ions thus preventing them from entering the
analyzer. As seen in our investigation this effect was not
simply correlated with specific parameter settings and
additional electronic feedback mechanisms might have
intensified or attenuated the primary effect.
Performance after system upgradeTo check the system performance after remedying the
electronic default and to differentiate between random
phenomena and systematic effects observed before the
system upgrade, several of the repeatability tests were
repeated under the same operating conditions as before,
except for the selection of an �1.0V hexapole RF lens bias.
Since data evaluation of reproducibilitymeasurements is still
in progress, the results of only two test series are presented
here that most clearly demonstrate differences in system
performance.
Table 6. Repetition of test series 3 (cf. Table 4) after MS
upgrade
Analyte
Single componentstandard (20 injections)
Multiple componentstandard (25 injections)
x %RSD %CoSa x %RSD %CoSa
Nitrite 2465 9.3 �10.4 597 13.1 þ15.8Nitrate 27603 8.7 þ9.9 24128 10.1 þ17.2Malonic acid 62268 8.3 �15.6 29218 10.3 þ10.9Mandelic acid 65069 6.6 þ8.5 22288 9.9 þ17.6
aChange in sensitivity: detector response for the last injection relatedto the first injection (both values derived from the linear regressionfunction).Conditions as described in Table 4
Copyright # 2006 John Wiley & Sons, Ltd.
The results from the repetition of test series 3 are combined
in Table 6. The RSD values for individual test sequences
spanned between 6.6% and 13.1%. The standard deviations
are not always smaller than those achieved with the first
application of the test scheme, but the data set is more
homogeneous in so far as extreme variabilities did not occur.
Furthermore, the RSDs of the separate injections of the
analytes are generally smaller than the injections of the
multiple component solution. In contrast to the first set of test
series, the detector sensitivity tended to increase with time
for most analytes. Nevertheless, the change in the detection
sensitivity is smaller than 20%, indicating a significant
improvement in the detector performance. Paralleling the
initial situation the mean detector response for nitrate is at
least one order of magnitude greater than for nitrite and the
mean peak areas of the separately injected compounds are
two- to four-fold greater than the jointly injected analytes,
except for nitrate. This result underlines that the use of mass
spectrometry does not reduce the necessity to separate the
analytes as completely as possible before detection.
The repetition of the tests with suppressor operation and
methanol addition confirmed dramatic improvements in
signal repeatability. As illustrated in Fig. 3(A), the order of
the various analytical conditions, ranked according to the
average nitrite peak area, is the same as before, but
the detector response is essentially more stable, especially
for the parameter setting ’with methanol/without suppres-
sor’. The same inference can be drawn from the data for
mandelic acid (Fig. 3(B)). For the two test series where the
suppressor was operated, the relative changes in sensitivity
wereþ0.4% (without methanol) andþ2.7% (with methanol),
respectively, compared with �93.5% and �81.3%, for the
initial situation. The worst result (�38.9%) was achieved
without suppressor operation and without methanol
addition. The new situation qualitatively parallels the earlier
in as far as the highest detection sensitivity for mandelic acid
(and now also for nitrate) was achieved with the operating
conditions ’methanol addition/inactivated suppressor’.
From the complete data set some correlations between
operational conditions and MS performance are now more
obvious than before. With respect to signal reproducibility
the parameter combination ’without methanol/without
suppressor’ yielded the worst results. Here the sensitivity
losses ranged from 26.8% to 38.9%. Using the suppressor a
Rapid Commun. Mass Spectrom. 2006; 20: 2419–2426
DOI: 10.1002/rcm
Figure 3. Repetition of the test scheme for the determination of the influence of methanol addition and
suppressor operation on MS response after MS upgrade. Conditions as in Fig. 2.
Examination of the signal area precision of an ELMO TSQTM 2425
sensitivity drift did not occur or was less than 5% in 5 out of 9
test sequences. In three cases only the drift was between 10%
and 15%. With one exception the RSD values were below
10%. Except for nitrite the addition of methanol increased
detection sensitivity.
CONCLUSIONS
The present results allow us to draw the following
conclusions:
1. E
Co
xtended signal area repeatability and reproducibility
tests were able to unambiguously identify an electronic
default of an ELMO MSQTM detector and they helped to
localize the cause of its malfunction. The same test scheme
confirmed significant improvements in the detector per-
formance after the default had been remedied. After
having technically upgraded the detector clear corre-
lations between FIA-MS operating conditions and system
pyright # 2006 John Wiley & Sons, Ltd.
performance were found, e.g. enhancement of the detec-
tion sensitivity by methanol addition and increase in
signal repeatability by suppressor operation. Further-
more, the repetition of the test scheme proved that several
of the earlier observed effects, e.g. the relatively low
detection sensitivity for nitrite, are of a systematic rather
than of a random nature.
2. A
ccording to Slingsby and Schnute,19 internal standardsshould be used when the mass spectrometer is used for
quantification in IC/ESI-MS methods. Without doubt
internal standards are valuable tools to correct for matrix
effects, e.g. ion suppression, and for short-time fluctu-
ations of other system properties, e.g. spray formation and
ion transmission efficiencies. There are several reasons
why their recommendation would not help to correct data
biased by a detector malfunction. First, the addition of one
internal standard assumes that all analytes are affected in
the same way and to the same extent by system perform-
ance variations. If this assumption is not valid, as in our
Rapid Commun. Mass Spectrom. 2006; 20: 2419–2426
DOI: 10.1002/rcm
Co
2426 K. Fischer, S. Hoffler and A. Meyer
case, a stable labeled standard has to be added for every
analyte and this can be quite expensive. Furthermore,
suitable standards are not commercially available for all
relevant substances. Secondly, internal standards cannot
compensate for a progressive deterioration of the signal-
to-noise ratio. Thirdly, in this specific context, the use of
internal standards can lead the user to adapt to the
problem instead of examining and solving it.
3. T
he instrument functional verification and installationacceptance tests are based on the measurement of the
signal-to-noise ratio of a sample three times consecutively
injected within a short time span. Depending on the
ionization mode, different samples, settings, and
parameters for qualification are specified. A second qual-
ity control criterion is delivered by the autotune process,
which tunes and calibrates the mass accuracy in the ESI
mode within the whole nominal mass range. Both pro-
cedures are not capable of detecting sensitivity drifts of
the mass spectrometer. Therefore, we strongly recom-
mend extending the installation acceptance procedure
by a test protocol suited to control the precision of the
mass spectrometer response. We suggest that the instru-
ment performance standards guaranteed by the manufac-
turer should be supplemented by a precision criterion.
According to our experiences the FIA-MS technique is
suited for the proposed test scheme. The test protocol
should encompass a minimum number of 30 replicate
injections within a time span of 6 h at least. The statistical
treatment of the data should include a method, e.g.
regression analysis, able to identify or exclude a possible
correlation between data variation and time at a given
significance level.
NOTICE
We do not claim that any other ELMO MSQTM apparatus
necessarily has or did have the same critical properties as our
instrument before its technical upgrade. Furthermore, we do
not claim that the observed properties do apply or did apply
to types ofMSQTM detectors (e.g. with square quadrupole RF
pyright # 2006 John Wiley & Sons, Ltd.
lenses), to ionization modes, to operating conditions, or to
analytes other than those used in this study.
Our instrument was installed in July 2003. The electric
fault was detected in autumn 2004 and fixed in January 2005.
It is likely that ELMO MSQTM detectors installed since the
latter date have undergone a technical development to
prevent the described phenomena.
AcknowledgementsThe authors would like to thank Prof. W. Buchberger for
critical comments on the manuscript.
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