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Acetonitrile and benzene in the breath of smokers and non-smokers investigated by proton transfer reaction mass spectrometry (PTR-MS)
ELSEVIER
International Journal of Mass Spectrometry and Ion Processes 148 (1995) L1-L3
and Ion Processes
Letter
Acetonitrile and benzene in the breath of smokers and non-smokers investigated by proton transfer reaction mass spectrometry (PTR-MS) A. Jordan, A. Hansel, R. Holzinger, W. L i n d i n g e r * Institut fiir lonenphysik, Universitiit Innsbruck, Technikerstr. 25, A-6020 Innsbruck, Austria
Received 6 June 1995; accepted 8 June 1995
Abstract Benzene and acetonitrile are both present in greater concentrations in the breath of smokers than in non-smokers. The concentrations of these neutrals can be readily detected in the gas phase by their proton transfer reactions with H3 O+. The concentration of benzene in the breath of smokers rapidly decreases with the time since the last cigarette was smoked, declining to values similar to those of non-smokers within an hour. In contrast, the concentration of acetonitrile in the breath of smokers takes nearly a week to decrease to that of non-somokers, once smoking stops. Thus the analysis of acetonitrile in the breath is a most suitable indicator of whether a given subject is or is not a smoker. Keywords: Acetonitrile; Benzene; Breath analysis; Non-smokers; Proton transfer reaction mass spectrometry (PTR-MS); Smokers
Recently it has been reported that the exhaled breath of cigarette smokers contains elevated concentrations of benzene compared to that of non-smokers. For example, the average concentration in smokers was reported to be (6.8 ± 3.0) ppb versus (2.5 + 0.8) ppb in non-smokers [1]. We have developed a method for the rapid analysis of breath components [2] based on the protonation of neutral components by the strong gas phase acid H30 + [3] and have used this method to study the time dependence of concentrations of benzene and acetonitrile in smokers and non-smokers. The * Corresponding author.
results of these experiments are reported below. Our use of proton transfer reactions to detect the components of human breath was first described for the detection of methanol, ethanol and acetone [2]. In these experiments we generated H3 O+ in a selected-ion flow drift tube and added the breath gases to be analysed into a 0.3 Torr flow drift tube of helium buffer gas. In the present experiment we have created H3 O+ ions in a plasma ion source using H 2 0 as the discharge gas. Under these conditions H3 O+ and H30+(HzO)n (n = 1, 2, 3) ions are formed. We then extract the ions at energies
0168-1176/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved S S D I 01 68-1176(95)04236-9
A. Jordon et al./lnternational Journal of Mass Spectrometry and Ion Processes 148 (1995) L I - L 3
L2
A e~
&30 " " 25 ~ 2o
30 no. smokers
20 co
Q.
~
"
N
..Q
10
"515 e-
0
.9 10 5
C
~105 IlIIIl. dl
i
smokers
' oL,flldm., .In 0 5 10 15 20
....
J
25 30
¢i.
• ,
I--I--I I
i
o -15 0 0
•
I
i
i
,
i
-
• I
i
I--I--I ,
i
i
-
.
15 30 45 60 75 Time (min)
Fig. 2. Concentration of benzene in the breath of two test persons smoking a cigarette before t = O.
Concentration of benzene (ppb) Fig. 1. Measured concentrations of benzene in the breath of 56 non-smokers and 75 smokers respectively. The mean + SD concentration in non-smokers is 3.25 ± 0.97 ppb, while that of smokers is significantly higher, 8.13 ± 5.59 ppb.
sufficiently high for the clustered ions H30+(H20)n to dissociate, so that only H3 O+ ions remain. These ions are then led into a drift tube in which the breath gases themselves are used as the buffer gas. In this way the sensitivity of detection of trace components is greatly enhanced. The instrumental details are reported in a separate publication [4], but the method of taking and reducing the data, however, is much the same as reported earlier [2]. As benzene has a higher proton affinity than water [5], H3 O+ reacts with benzene on every collision to form C6H ~- at mass 79 as the only ionic product. Knowing the rate coefficient for this proton transfer reaction, one can easily calculate the concentration of neutral benzene from the measured count rates of C6H ~- and H3 O+ [2,4]. When we analyse different samples of the breath of a single individual taken over a few minutes the reproducibility of the analysis is typically + 20%. The details are discussed in Refs. [2,4]. Fig. 1 shows the benzene concentrations in units of ppb in 75 smokers and 56 nonsmokers. The mean + SD (standard deviation) concentration in non-smokers is 3.25 4-0.97 ppb, while that of smokers is significantly
higher, averaging 8.13 + 5.59 ppb. In smokers, however, the benzene concentration is extremely time dependent, falling rapidly with time since the last smoking of a cigarette. As Fig. 2 shows, immediately before smoking the cigarette the concentration of benzene in the breath of a smoker is essentially indistinguishable from the concentration in non-smokers. Right after the smoking of a single cigarette, the benzene concentration rises dramatically and then returns to normal over the next hour. Thus the quantity of benzene which will be detected in the breath depends strongly on the time since the last episode of smoking by the subject, which is reflected in the large standard deviation (4-5.59 ppb). Therefore the concentration of benzene in the breath is not a useful indicator 40-
I II
30-
smokers I non smokers
'~ 20
"~ 10z
I,
/ . , d l l i.
.~Uml | ~ I
Ih.
i I
.I . . . . .
,
I
50 100 150 200 Concentration of acetonitrile (ppb) Fig. 3. Measured concentrations of acetonitrile in the breath of 77 non-smokers and 82 smokers respectively. The mean + SD concentration in non-smokers is 5.65 ± 1.90 ppb, while that of smokers is dramatically higher 69.33 -4- 33.34 ppb.
A. Jordan et al./lnternational Journal of Mass Spectrometry and Ion Processes 148 (1995) L1-L3 lOO I
8O 6O "6
4O 2O
0 0 0
24 48 72 96 120 144 168 Time (hours)
Fig. 4. Concentration of acetonitrile in the exhaled breath of a smoker as a function of time. At 0 h, smoking was stopped.
of whether or not an individual is a smoker or not. Simultaneously with our analysis of benzene we also analysed the breath of smokers and non-smokers for the presence of acetonitrile (CH3CN). Proton transfer of H3 O+ to this neutral to form an ion of mass 42 is also quantitative and extremely rapid [6]. The results for this analysis are given in Fig. 3 and show much more dramatic differences between smokers and non-smokers. The nonsmokers all have acetonitrile concentrations of less than 15 ppb, while smokers have a minim u m of about 30 ppb and can reach values up to 200 ppb. The acetonitrile concentration as a function of time since the last smoking of a cigarette also differs strongly from that of benzene, as is shown in Fig. 4. A smoker establishes a high and almost steady state concentration of acetonitrile in the breath, which decreases only slowly with time when smoking stops. A test smoker who averages smoking 20
L3
cigarettes per day had established an average concentration of about 90 ppb of acetonitrile in his breath. Its concentration dropped only slowly when smoking ceased. Twenty-four hours later the acetonitrile concentration had dropped only to 50 ppb, and it took nearly a week for the concentration to drop to approximately that of the nonsmoking population. Thus the analysis of acetonitrile in the breath would be a much better indicator than that of benzene of whether a given subject is or is not a smoker. It is striking that the acetonitrile concentration in the breath of non-smokers is considerably higher than in ambient air (we never observed values higher than 1 ppb) which suggests an addition, probably endogenic, source of acetonitrile. The same is true for benzene, as was reported by Wester et al. [1], a finding which was also confirmed in the present investigation.
References [1] R.C. Wester, H.I. Maibach, L.D. Gruenke and J.C. Craig, J. Toxicol. Environ. Health, 18 (1986) 567. [2] A. Lagg, J. Taucher, A. Hansel and W. Lindinger, Int. J. Mass Spectrom. Ion Processes, 134 (1994) 55. [3] A.P. Bruins, in J.F. Todd (Ed.), Advances in Mass Spectrometry, Wiley, 1985, pp. 119-131. [4] A. Hansel, A. Jordan, R. Holzinger, R. Prazeller, W. Vogel and W. Lindinger, in preparation. [5] S.G. Lias, J.F. Liebman and R.D. Levin, J. Phys. Chem. Ref. Data, 13 (1984) 695. [6] V.G. Anicich, J. Phys, Chem. Ref. Data, 22 (1993) 1469.
International Journal of Mass Spectrometry and Ion Processes 148 (1995) L1-L3
and Ion Processes
Letter
Acetonitrile and benzene in the breath of smokers and non-smokers investigated by proton transfer reaction mass spectrometry (PTR-MS) A. Jordan, A. Hansel, R. Holzinger, W. L i n d i n g e r * Institut fiir lonenphysik, Universitiit Innsbruck, Technikerstr. 25, A-6020 Innsbruck, Austria
Received 6 June 1995; accepted 8 June 1995
Abstract Benzene and acetonitrile are both present in greater concentrations in the breath of smokers than in non-smokers. The concentrations of these neutrals can be readily detected in the gas phase by their proton transfer reactions with H3 O+. The concentration of benzene in the breath of smokers rapidly decreases with the time since the last cigarette was smoked, declining to values similar to those of non-smokers within an hour. In contrast, the concentration of acetonitrile in the breath of smokers takes nearly a week to decrease to that of non-somokers, once smoking stops. Thus the analysis of acetonitrile in the breath is a most suitable indicator of whether a given subject is or is not a smoker. Keywords: Acetonitrile; Benzene; Breath analysis; Non-smokers; Proton transfer reaction mass spectrometry (PTR-MS); Smokers
Recently it has been reported that the exhaled breath of cigarette smokers contains elevated concentrations of benzene compared to that of non-smokers. For example, the average concentration in smokers was reported to be (6.8 ± 3.0) ppb versus (2.5 + 0.8) ppb in non-smokers [1]. We have developed a method for the rapid analysis of breath components [2] based on the protonation of neutral components by the strong gas phase acid H30 + [3] and have used this method to study the time dependence of concentrations of benzene and acetonitrile in smokers and non-smokers. The * Corresponding author.
results of these experiments are reported below. Our use of proton transfer reactions to detect the components of human breath was first described for the detection of methanol, ethanol and acetone [2]. In these experiments we generated H3 O+ in a selected-ion flow drift tube and added the breath gases to be analysed into a 0.3 Torr flow drift tube of helium buffer gas. In the present experiment we have created H3 O+ ions in a plasma ion source using H 2 0 as the discharge gas. Under these conditions H3 O+ and H30+(HzO)n (n = 1, 2, 3) ions are formed. We then extract the ions at energies
0168-1176/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved S S D I 01 68-1176(95)04236-9
A. Jordon et al./lnternational Journal of Mass Spectrometry and Ion Processes 148 (1995) L I - L 3
L2
A e~
&30 " " 25 ~ 2o
30 no. smokers
20 co
Q.
~
"
N
..Q
10
"515 e-
0
.9 10 5
C
~105 IlIIIl. dl
i
smokers
' oL,flldm., .In 0 5 10 15 20
....
J
25 30
¢i.
• ,
I--I--I I
i
o -15 0 0
•
I
i
i
,
i
-
• I
i
I--I--I ,
i
i
-
.
15 30 45 60 75 Time (min)
Fig. 2. Concentration of benzene in the breath of two test persons smoking a cigarette before t = O.
Concentration of benzene (ppb) Fig. 1. Measured concentrations of benzene in the breath of 56 non-smokers and 75 smokers respectively. The mean + SD concentration in non-smokers is 3.25 ± 0.97 ppb, while that of smokers is significantly higher, 8.13 ± 5.59 ppb.
sufficiently high for the clustered ions H30+(H20)n to dissociate, so that only H3 O+ ions remain. These ions are then led into a drift tube in which the breath gases themselves are used as the buffer gas. In this way the sensitivity of detection of trace components is greatly enhanced. The instrumental details are reported in a separate publication [4], but the method of taking and reducing the data, however, is much the same as reported earlier [2]. As benzene has a higher proton affinity than water [5], H3 O+ reacts with benzene on every collision to form C6H ~- at mass 79 as the only ionic product. Knowing the rate coefficient for this proton transfer reaction, one can easily calculate the concentration of neutral benzene from the measured count rates of C6H ~- and H3 O+ [2,4]. When we analyse different samples of the breath of a single individual taken over a few minutes the reproducibility of the analysis is typically + 20%. The details are discussed in Refs. [2,4]. Fig. 1 shows the benzene concentrations in units of ppb in 75 smokers and 56 nonsmokers. The mean + SD (standard deviation) concentration in non-smokers is 3.25 4-0.97 ppb, while that of smokers is significantly
higher, averaging 8.13 + 5.59 ppb. In smokers, however, the benzene concentration is extremely time dependent, falling rapidly with time since the last smoking of a cigarette. As Fig. 2 shows, immediately before smoking the cigarette the concentration of benzene in the breath of a smoker is essentially indistinguishable from the concentration in non-smokers. Right after the smoking of a single cigarette, the benzene concentration rises dramatically and then returns to normal over the next hour. Thus the quantity of benzene which will be detected in the breath depends strongly on the time since the last episode of smoking by the subject, which is reflected in the large standard deviation (4-5.59 ppb). Therefore the concentration of benzene in the breath is not a useful indicator 40-
I II
30-
smokers I non smokers
'~ 20
"~ 10z
I,
/ . , d l l i.
.~Uml | ~ I
Ih.
i I
.I . . . . .
,
I
50 100 150 200 Concentration of acetonitrile (ppb) Fig. 3. Measured concentrations of acetonitrile in the breath of 77 non-smokers and 82 smokers respectively. The mean + SD concentration in non-smokers is 5.65 ± 1.90 ppb, while that of smokers is dramatically higher 69.33 -4- 33.34 ppb.
A. Jordan et al./lnternational Journal of Mass Spectrometry and Ion Processes 148 (1995) L1-L3 lOO I
8O 6O "6
4O 2O
0 0 0
24 48 72 96 120 144 168 Time (hours)
Fig. 4. Concentration of acetonitrile in the exhaled breath of a smoker as a function of time. At 0 h, smoking was stopped.
of whether or not an individual is a smoker or not. Simultaneously with our analysis of benzene we also analysed the breath of smokers and non-smokers for the presence of acetonitrile (CH3CN). Proton transfer of H3 O+ to this neutral to form an ion of mass 42 is also quantitative and extremely rapid [6]. The results for this analysis are given in Fig. 3 and show much more dramatic differences between smokers and non-smokers. The nonsmokers all have acetonitrile concentrations of less than 15 ppb, while smokers have a minim u m of about 30 ppb and can reach values up to 200 ppb. The acetonitrile concentration as a function of time since the last smoking of a cigarette also differs strongly from that of benzene, as is shown in Fig. 4. A smoker establishes a high and almost steady state concentration of acetonitrile in the breath, which decreases only slowly with time when smoking stops. A test smoker who averages smoking 20
L3
cigarettes per day had established an average concentration of about 90 ppb of acetonitrile in his breath. Its concentration dropped only slowly when smoking ceased. Twenty-four hours later the acetonitrile concentration had dropped only to 50 ppb, and it took nearly a week for the concentration to drop to approximately that of the nonsmoking population. Thus the analysis of acetonitrile in the breath would be a much better indicator than that of benzene of whether a given subject is or is not a smoker. It is striking that the acetonitrile concentration in the breath of non-smokers is considerably higher than in ambient air (we never observed values higher than 1 ppb) which suggests an addition, probably endogenic, source of acetonitrile. The same is true for benzene, as was reported by Wester et al. [1], a finding which was also confirmed in the present investigation.
References [1] R.C. Wester, H.I. Maibach, L.D. Gruenke and J.C. Craig, J. Toxicol. Environ. Health, 18 (1986) 567. [2] A. Lagg, J. Taucher, A. Hansel and W. Lindinger, Int. J. Mass Spectrom. Ion Processes, 134 (1994) 55. [3] A.P. Bruins, in J.F. Todd (Ed.), Advances in Mass Spectrometry, Wiley, 1985, pp. 119-131. [4] A. Hansel, A. Jordan, R. Holzinger, R. Prazeller, W. Vogel and W. Lindinger, in preparation. [5] S.G. Lias, J.F. Liebman and R.D. Levin, J. Phys. Chem. Ref. Data, 13 (1984) 695. [6] V.G. Anicich, J. Phys, Chem. Ref. Data, 22 (1993) 1469.