Determination of Thallium in Brain Tissue by Stable Isotope
Dilution and Field Desorption Mass Spectrometry *
H.-R. Schulten, W . D. Lehmann
Institute of Physical Chemistry, University of Bonn, and
R. Ziskoven
Institute of Physiology II, University of Bonn
Z. Naturforsch. 33 c, 484 — 487 (’1978) ; received June 2, 1978
M ass Spectrometry, Field Desorption, M etal Cations, Isotope Dilution, Tissue Analysis
The utility of field desorption mass spectrometry for quantitative metal cation analysis in
forensic sciences is demonstrated by the determination of a lethal thallium level in the brain tissue
of an experimental animal. Stable isotope dilution and accumulation of the electrically recorded
field desorption ion currents with a multi-channel analyzer allowed a direct estimation of thallium
in homogenized tissue samples without further pretreatment. Experim ents with standard solutions
revealed the limit of detection for thallium to be about 10 p g of the metal cation.
and cadmium [ 11 ], and in this study also to thallium.
Introduction
The heavy metal thallium has a pronounced toxic
effect on mammals. Poisonings by thallium ions
norm ally proceed very slow ly; they are accompanied
by loss o f hair, severe polyneuritic symptoms, and
tachycardia, and can culminate in paralysis o f the
central nervous system [ 1 ] .
A tom ic
absorption is a common
spectroscopic
In particular, we were interested in a possible ap­
plication o f FD MS in forensic or other medical
sciences which requires a reliable, sensitive, and
fast determination o f thallium in biological fluids
and tissues.
Experim ental
method fo r the determination o f thallium and is
capable
of
determining
thallium
concentrations
down to a few ppm [ 2 ] .
A mouse was fed a portion o f cheese containing
80 mg o f thallium chloride. A fter the animal’ s death
(5 hours after application) the brain was removed
The direct determination of thallium from human
urine showed a lim it o f detection o f approxim ately
( 0.20 g ) , homogenized with about
1
ml o f doubly
distilled water, and then further diluted to give
30 ppb, whereas direct estimation from plasma and
2.0 ml o f a suspension. For the preparation of the
brain tissue was not successful without pretreatment
solution o f the internal standard isotopically enrich­
[3 ].
Field desorption (F D ) mass spectrometry (M S ),
ed elemental thallium (Rohstoff-Einfuhr GmbH und
origin ally introduced fo r soft ionization o f organic
was dissolved in
compounds o f low volatility [4, 5 ], has proven to
concentration o f
Handelsgesellschaft Ost, Düsseldorf, W .-Germ any)
to
on a double focussing mass spectrometer o f type
In continuation o f our efforts to exploit the
Varian M A T 731 equipped with a combined EI/FI/
analysis, especially fo r alkali determinations
9 ].
to give a thallium
The mass spectrometric studies were perform ed
be an extremely sensitive technique fo r metal cation
[6
0.1 m nitric acid
1 mmole/liter.
capacity o f FD M S as an additional independent
FD ion source and, alternatively, on a home-built
method fo r metal cation analysis we applied this
single-focussing FD mass spectrometer. The emitters
novel mass spectrometric technique to
used were
a number
10 jum
diameter tungsten wires activated
o f elements from the second series in the periodic
at high temperature with an average length o f the
[ 10 ] ,
microneedles of 30 jum. The samples were applied
system, such as calcium, strontium, barium
by the syringe technique and
2 ju\
of sample solution
were used fo r one analysis on average. The FD ion
* Quantitative Field Desorption M ass
11; for Part 10 see ref. [7 ].
Spectrometry:
Part
Requests for reprints should be sent to Dr. H .-R . Schulten,
Institut für Physikalische Chemie der Universität W egelerstraße 12, D-5300 Bonn.
currents were recorded electrically and accumulated
by
a
multi-channel
analyzer
of
type
CAT-1024
Varian which was triggered from the cyclic magnet­
ic scan o f the mass spectrometer [ 12 ].
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485
H.-R. Schulten et al. • Determination of Thallium in Brain Tissue by Stable Isotope Dilution
R esu lts and D iscussion
Since thallium naturally occurs as a m ixture o f
two stable isotopes and since isotopically enriched
thallium is com m ercially available, stable isotope
dilution appears to be the method o f choice fo r a
mass spectrometric quantitation. The utility o f this
Fig. 2. Isotope dilution experi­
ment for the determination of
thallium in a mouse brain
homogenizate. The sample was
diluted 1 :1 with the standard
solution (F ig. 1 b ) . The isotopic
abundances are: m /e 203 70.0%,
m le 205 30.0%. 80 Scans were
accumulated.
technique o f internal standardization fo r quantita­
tive studies by field desorption mass spectrometry
has been demonstrated fo r a number o f organic
compounds [1 3 ] as well as fo r organic [1 4 ] and
inorganic cations [1 5 ]. Coupling o f the mass spec­
trometer to a multi-channel analyzer is especially
advantageous
fo r
these
investigations
because
it
allows integrating electrical recording o f the FD
ions in the mode o f repetitive scanning. Thus the
fluctuations o f the FD ion currents can be com ­
pensated effectively and quantitative data o f good
precision are obtained. Fig. 1 shows the isotopic
Thus, only 0.3% o f the total amount o f thallium ap­
abundances of naturally occuring thallium, o f the
plied could be determined in the brain tissue.
isotopically enriched thallium standard, and o f a
model mixture measured by this procedure.
F or the quantitative determination o f thallium in
the homogenizate o f mouse brain tissue an aliquot
o f this sample was diluted
1:1
The slow time scale o f thallium poisonings and
the relatively low amount o f thallium found in this
study indicate that the toxic metal is transported
slow ly into the brain tissue.
with our thallium
Although the desorption o f thallium occurs at
standard solution. The result o f the thallium iso­
relatively low emitter heating currents (20 — 25 m A )
tope analysis perform ed on this mixture is display­
no interference from organic ions could be observed
ed in Fig. 2.
in the investigation o f the brain tissue homogenizate.
Evaluation o f the data from Fig. 2 revealed a
thallium
concentration
4.0 ± 0.3 //mol/g
0.8 ±
fresh
in
the
weight,
0.06 //mol thallium
in
the
F o r a FD mass spectrometric investigation, however,
mouse
brain
of
which
results
in
as compared to sample amounts usually required
brain.
fo r an alkali determination. In order to determine
complete
the concentration o f about 90 ng//d thallium is high
c)
F ig. 1. Isotopic abundances of thallium
recorded by F D M S and signal accum ula­
tion. For each measurement 120 cyclic
magnetic scans were accumulated.
a) natural abundances of thallium, m /e
203 29.5%, m le 205 70.5%.
b ) stable isotope enriched internal stan­
dard, m le 203 87.0%, m /e 205 13.0%.
c) model mixture of equim olar amounts of
a) and b ) m je 203 58.5%, m je 205 41.5%.
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486
the
H.-R. Schulten et al. • Determination of Thallium in Brain Tissue by Stable Isotope Dilution
sensitivity
of
amounts between
FD
MS
fo r
10 ng
and
10 pg
thallium,
sample
£ 0 5 tI] +
thallium dissolv­
ed in distilled water were applied to the FD emitter
and completely desorbed. During the whole desorp­
tion the FD ion currents in the mass region m je
200
— m/e 208 were accumulated by the use o f
the multichannel analyzer. The results o f this study
are displayed in F ig. 3.
peak height
[203Ti] +
10pg Thallium on em itter
102 -
F ig. 4. O rigin al recording for the analysis of 10 p g of thal­
lium
50 fm ol) by F D M S . 25 scans were accumulated.
a rb itra ry
u nits
rolyzed and destroyed to a large extent whereas at
noise level
heating currents favourable fo r thallium (ca.
20
to
25 m A ) interference from organic ion species might
hamper an extrem ely sensitive detection.
T h a lliu m
C on clu sion
on e m itte r
F ig. 3. Accum ulated peak heights of the thallium isotope at
m/e 203 (29.5% natural abundance) as a function of the
total sample amount of thallium desorbed in one F D
analysis.
F ield desorption mass spectrometry appears to
be a reliable, sensitive, and fast method fo r the
determination
of
thallium
in
b iological
samples.
In particular, the use o f a stable isotope labelled
internal standard and the possibility o f analyzing
The original plot obtained fo r the analysis of
10 pg o f thallium is shown in Fig. 4.
untreated samples are important advantages o f the
method. Finally, the sensitivity o f field desorption
Due to the relatively high atomic weight o f thal­
fo r thallium appears to be o f the same order as fo r
lium this corresponds to only about 50 fm ol. These
alkali metals, which enables its determination in
studies show that thallium can be analyzed by FD
trace and ultratrace quantities.
with essentially the same sensitivity as metals from
This work was financially supported by the Deut­
the alkali series which is consistent with the marked
sche Forschungsgemeinschaft, the M inisterium für
sim ilarity o f thallium and potassium with respect
Wissenschaft und Forschung des Landes Nordrhein-
to their ion radii and their chemical properties.
W estfalen and the Fond der Deutschen Chemischen
H ow ever, in the analysis o f untreated biological
Industrie.
cations
W e are very grateful to E. Pascher, M ikroanalyti­
might be larger since these cations desorb at higher
sches Laboratorium , Bonn, fo r his efforts to deter­
emitter heating currents (ca. 30 — 1 0 0 m A ). Under
mine thallium in our samples by atomic absorption
these conditions the organic matrix is already py-
spectroscopy.
samples
[1 ]
[2 ]
[3 ]
[4 ]
the
actual
sensitivity
fo r
alkali
F. Hauschild, Pharm okologie und Grundlagen der
Toxilogie, V E B Thieme, Leipzig 1973.
B. W elz, Atomabsorptions-Spektroskopie, V e rla g Che­
mie, W einheim 1975
E. Pascher, Bonn, unpublished results.
H. D. Beckey, Principles of Field Ionization and Field
Desorption M ass Spectrometry, Pergam on Press, O x ­
ford 1977.
[5 ]
[ 6]
[7 ]
[ 8]
H .-R . Schulten, in M ethods of Biochemical Analysis,
(D . Glick, e d .), V o l. 24, p. 313, Wiley-Interscience,
N ew Y ork 1977.
W . D. Lehm ann and H .-R . Schulten, A n al. Chem. 49,
1744 (1 977).
H.-R . Schulten, R. Ziskoven, and W . D. Lehmann,
Z. Naturforsch. 33 c, 178 (1 978).
R. Ziskoven, Thesis 1978.
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H .-R . Schulten et al. • Detenmination of Thallium in B rain Tissue by Stable Isotope Dilution
[9] W . D. Lehmann, U. Bahr, H.-R. Schulten, Biomed.
iMass Spectrom. 5, X X X (1978).
[10] H.-R. Schulten, W . D. Lehmann, and D. Haaks, Org.
Mass Spectrom. 13, 361 (1978).
[11] H.-R. Schulten and W . D. Lehmann, in Quantitative
Mass Spectrometry in L ife Sciences II, (Eds. A . P.
de Leenmeer, R. Roncucci, C. van Peteghem ), Else­
vier Scientific Publ., Amsterdam 1978.
487
[12] W . D. Lehmann, H.-R. Schulten, and H. M. Schiebel,
Z. Anal. Chem. 289, 1 1 (1978).
[il3 ] W . D. Lehmann and H.-R. Schulten, Biomed. Mass
Spectrom. 5, 208 (1978).
[14] W . D. Lehmann, H.-R. Schulten, and N . Schröder,
Biomed. Mass Spectrom. in press.
[15] W . D. Lehmann and H.-R. Schulten, Angew. Chem.
89, 890 (1977) ; Angew. Chem. Int. Ed. Engl. 16,
852 (1977).
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