Identification of Relatively High Molecular Weight Compounds in Human Breath Using Secondary Nano Electrospray Ionization Ultrahigh Resolution Mass Spectrometry†

doi:10.7503/cjcu20160821

Abstract

Abstract:

Human breath contains thousands of volatile organic compounds(VOCs), which would be potentially helpful for studying disease diagnosis and environmental exposure. However, owing to limitations in current analytical methods, only the compounds with molecular weights <300 have been widely reported in exhaled human breath. In this study, a high performance homemade secondary nanoelectrospray ionization source coupled with ultrahigh resolution mass spectrometer(nanoSESI-UHRMS) was set up and applied to investigating the presence of compounds with relatively high molecular weight(RHMW)(300—500) in healthy human breath. The results indicated that 29 RHMW compounds have been detected in real time by nanoSESI-UHRMS. These organic compounds mostly consist of C, H, N and O atoms, and the average of ring-double bond equivalent(RDB) values is (4.5±3.1), implying they are most likely to be ketones, aldehydes and fatty acids. These unsaturated compounds are characterized with high ionization efficiency in SESI, and thus readily detected by nanoSESI-UHRMS.

Key words: Human breath, Relative high molecular weight compound, Direct mass spectrometric analysis, Secondary electrospray ionization, Ultrahigh resolution

CLC Number:

O657.63

TrendMD:

HUANG Lei, LI Xue, XU Meng, HUANG Zhengxu, ZHOU Zhen. Identification of Relatively High Molecular Weight Compounds in Human Breath Using Secondary Nano Electrospray Ionization Ultrahigh Resolution Mass Spectrometry^†[J]. Chem. J. Chinese Universities, 2017, 38(5): 752.

Figures/Tables 6

Fig.1 Extracted ion chromatograms of three unknown compounds shown peaks at m/z 391.2829(a), 380.3375(b) and 336.2032(c) for five replicated measurements

Fig.2 Background-subtracted mass spectra(m/z 300—500) of exhaled breath of a subject under positive(A) and negative(B) ion detection modes

Fig.3 Background-subtracted mass spectra of isobaric ions m/z 300.1806, 300.2170, 300.2535 and 300.2896 at R values of 1.2×105(solid line) and 1.5×104(short dash line)

Fig.4 Six replicate measurements of m/z 300.2170 at resolutions of 1.2×105(A) and 1.5×104(B)

Fig.5 Six replicate measurements of m/z 300.2896 at resolutions of 1.2×105(A) and 1.5×104(B)

Table 1 Identification of 29 compounds in the range of m/z 300—500 from breath samples of 4 subjects

Compound	m/z	Detection mode	Composition	RDB^a	S1^b	S2^b	S3^b	S4^b
1	300.2896	Positive	C₁₈H₃₈NO₂	0.5	Det.^c	ND^d	Det.	Det.
2	301.2385	Negative	$C 1 7 H 3 3$ O₄	1.5	Det.	Det.	Det.	Det.
3	312.1806	Positive	C₁₆H₂₆NO₅	4.5	Det.	Det.	Det.	ND
4	322.1865	Positive	C₁₄H₂₈NO₇	1.5	ND	ND	ND	Det.
5	324.2170	Positive	C₁₈H₃₀NO₄	4.5	Det.	Det.	Det.	Det.
6	332.9061	Negative			ND	ND	Det.	ND
7	334.9033	Negative			ND	ND	Det.	ND
8	336.2032	Positive	C₁₅H₃₀NO₇	1.5	Det.	Det.	Det.	Det.
9	338.1675	Positive			Det.	ND	ND	Det.
10	338.2328	Positive	C₁₉H₃₂NO₄	4.5	Det.	Det.	Det.	Det.
11	339.5948	Negative			Det.	ND	Det.	ND
12	346.0331	Positive			ND	ND	Det.	ND
13	346.1862	Positive	C₁₆H₂₈NO₇	3.5	Det.	ND	ND	ND
14	348.2170	Positive	C₂₀H₃₀NO₄	6.5	Det.	Det.	Det.	Det.
15	352.2483	Positive	C₂₀H₃₄NO₄	4.5	Det.	ND	ND	Det.
16	356.2797	Positive	C₂₀H₃₈NO₄	2.5	Det.	Det.	Det.	Det.
17	358.2016	Positive	C₂₁H₂₈NO₄	8.5	ND	Det.	Det.	Det.
18	363.3107	Positive	C₂₀H₄₃O₅	-0.5	Det.	Det.	Det.	Det.
			C₁₉H₃₇N₇	5.0	Det.	Det.	Det.	Det.
19	373.8173	Negative			Det.	ND	Det.	Det.
20	378.9106	Negative			ND	Det.	Det.	ND
21	380.3375	Positive	C₁₉H₄₀N₈	4.0	Det.	Det.	Det.	Det.
22	380.9078	Negative			ND	Det.	Det.	ND
23	382.9049	Negative			ND	Det.	ND	ND
24	386.0830	Positive	C₁₂H₁₄N₆O₉	9.0	Det.	ND	ND	Det.
25	388.0789	Positive	C₁₉H₁₆O₉	12.0	Det.	ND	ND	Det.
26	391.2829	Positive	C₂₄H₃₉O₄	5.5	Det.	Det.	Det.	Det.
27	452.3952	Positive	C₂₃H₄₈N₈O	4.0	Det.	Det.	Det.	Det.
28	462.1468	Positive	C₁₂H₄₀NO₆Si₆	-0.5	ND	ND	Det.	ND
29	464.1280	Positive	C₁₅H₂₂N₅O₁₂	7.5	ND	ND	Det.	ND

Table 1 Identification of 29 compounds in the range of m/z 300—500 from breath samples of 4 subjects

Compound	m/z	Detection mode	Composition	RDB^a	S1^b	S2^b	S3^b	S4^b
1	300.2896	Positive	C₁₈H₃₈NO₂	0.5	Det.^c	ND^d	Det.	Det.
2	301.2385	Negative	$C 1 7 H 3 3$ O₄	1.5	Det.	Det.	Det.	Det.
3	312.1806	Positive	C₁₆H₂₆NO₅	4.5	Det.	Det.	Det.	ND
4	322.1865	Positive	C₁₄H₂₈NO₇	1.5	ND	ND	ND	Det.
5	324.2170	Positive	C₁₈H₃₀NO₄	4.5	Det.	Det.	Det.	Det.
6	332.9061	Negative			ND	ND	Det.	ND
7	334.9033	Negative			ND	ND	Det.	ND
8	336.2032	Positive	C₁₅H₃₀NO₇	1.5	Det.	Det.	Det.	Det.
9	338.1675	Positive			Det.	ND	ND	Det.
10	338.2328	Positive	C₁₉H₃₂NO₄	4.5	Det.	Det.	Det.	Det.
11	339.5948	Negative			Det.	ND	Det.	ND
12	346.0331	Positive			ND	ND	Det.	ND
13	346.1862	Positive	C₁₆H₂₈NO₇	3.5	Det.	ND	ND	ND
14	348.2170	Positive	C₂₀H₃₀NO₄	6.5	Det.	Det.	Det.	Det.
15	352.2483	Positive	C₂₀H₃₄NO₄	4.5	Det.	ND	ND	Det.
16	356.2797	Positive	C₂₀H₃₈NO₄	2.5	Det.	Det.	Det.	Det.
17	358.2016	Positive	C₂₁H₂₈NO₄	8.5	ND	Det.	Det.	Det.
18	363.3107	Positive	C₂₀H₄₃O₅	-0.5	Det.	Det.	Det.	Det.
			C₁₉H₃₇N₇	5.0	Det.	Det.	Det.	Det.
19	373.8173	Negative			Det.	ND	Det.	Det.
20	378.9106	Negative			ND	Det.	Det.	ND
21	380.3375	Positive	C₁₉H₄₀N₈	4.0	Det.	Det.	Det.	Det.
22	380.9078	Negative			ND	Det.	Det.	ND
23	382.9049	Negative			ND	Det.	ND	ND
24	386.0830	Positive	C₁₂H₁₄N₆O₉	9.0	Det.	ND	ND	Det.
25	388.0789	Positive	C₁₉H₁₆O₉	12.0	Det.	ND	ND	Det.
26	391.2829	Positive	C₂₄H₃₉O₄	5.5	Det.	Det.	Det.	Det.
27	452.3952	Positive	C₂₃H₄₈N₈O	4.0	Det.	Det.	Det.	Det.
28	462.1468	Positive	C₁₂H₄₀NO₆Si₆	-0.5	ND	ND	Det.	ND
29	464.1280	Positive	C₁₅H₂₂N₅O₁₂	7.5	ND	ND	Det.	ND

References 27

[1]	Pleil J. D., Stiegel M. A., Anal. Chem., 2013, 85, 9984—9990
[2]	de Lacy C. B., Amann A., Al-Kateb H., Flynn C., Filipiak W., Khalid T., Osborne D., Ratcliffe N. M., J. Breath Res., 2014, 8, 911—922
[3]	Phillips M., Gleeson K., Hughes J.M. B., Greenberg J., Cataneo R. N., Baker L., McVay W. P., Lancet, 1999, 353, 1930—1933
[4]	Peng G., Tisch U., Adams O., Hakim M., Shehada N., Broza Y. Y., Billan S., Abdah-Bortnyak R., Kuten A., Haick H., Nature Nanotech., 2009, 4, 669—673
[5]	Pleil J. D., Fisher J. W., Lindstrom A. B., Environ. Health Perspect., 1998, 106, 573—580
[6]	Pleil J. D., Stiegel M. A., Anal. Chem., 2013, 85, 9984—9990
[7]	Vereb H., Dietrich A. M., Alfeeli B., Agah M., Environ. Sci. Technol., 2011, 45, 8167—8175
[8]	Bajtarevic A., Ager C., Pienz M., Klieber M., Schwarz K., Ligor M., Ligor T., Filipiak W., Denz H., Fiegl M., Hilbe W., Weiss W., Lukas P., Jamnig H., Hackl M., Haidenberger A., Buszewski B., Miekisch W., Schubert J., Amann A., BMC Cancer, 2009, 9, 1—16
[9]	Shen C. Y., Li J. Q., Wang H. Z., Zhi Z. H., Wang H. M., Huang C. Q., Liu S., Jiang H. H., Chu Y. N., Chinese J. Anal. Chem., 2012, 40(5), 773—777
	(沈成银, 李建权, 王宏志, 志中华, 王鸿梅, 黄超群, 刘升, 江海河, 储焰南.分析化学, 2012,40(5), 773—777)
[10]	Shen C. Y., Wang H. M., Huang C. Q., Lu Y., Xia L., Chen X. J., Wang H. Z., Chu Y. N., Chem. J. Chinese Universities, 2015, 36(2), 236—240
	(沈成银, 王鸿梅, 黄超群, 陆燕, 夏磊, 陈小景, 王宏志, 储焰南.高等学校化学学报, 2015,36(2), 236—240)
[11]	Endre Z. H., Pickering J. W., Storer M. K., Hu W. P., Moorhead K. T., Allardyce R., McGregor D. O., Scotter J. M., Physiol. Meas., 2011, 32, 115—130
[12]	Smith D., Wang T. S., Pysanenko A., Španěl P., Rapid Commun. Mass Spectrom., 2008, 22, 783—789
[13]	Turner C., Španěl P., Smith D., Physiol. Meas., 2006, 27, 321—337
[14]	Zeng Q., Li P. H., Cai Y. F., Zhou W., Wang H. D., Luo J., Ding J. H., Chen H. W., J. Breath Res., 2016, 10, 016008
[15]	Chen H. W., Wortmann A., Zhang W. H., Zenobi R., Angew. Chem. Int. Ed., 2007, 46, 580—583
[16]	Li X., Sinues P. M. L., Dallmann R., Bregy L., Hollmén M., Proulx S., Brown S. A., Detma M., Kohler M., Zenobi R., Angew. Chem. Int. Ed., 2015, 54, 7815—7818
[17]	Martinez-Lozano Sinues P., Kohler M., Zenobi R., Anal. Chem., 2013, 85, 369—373
[18]	Benoit F. M., Davidson W. R., Lovett A. M., Nacson S., Ngo A., Int. Arch. Occup. Environ. Health, 1985, 55, 113—120
[19]	Benoit F. M., Davidson W. R., Lovett A. M., Ngo A., Anal. Chem., 1983, 55, 805—807
[20]	Bregy L., Sinues P. M. L., Nudnova M. M., Zenobi R., J. Breath Res., 2014, 8, 027102
[21]	Li X., Huang L., Zhu H., Zhou Z., Rapid Commun. Mass Spectrom., 2016, 31, 301—308
[22]	Martinez-Lozano Sinues P., Malcolm K., Brown S. A., Zenobi R., Dallmann R., Chem. Commun., 2017, 53, 2264—2267
[23]	García-Gómez D., Gaisl T., Bregy L., Cremonesi A., Martinez-Lozano Sinues P., Kohler M., Zenobi R., Clin. Chem., 2016, 62, 1230—1237
[24]	García-Gómez D., Gaisl T., Bregy L., Martinez-Lozano Sinues P., Kohler M., Zenobi R., Chem. Commun., 2016, 52, 8526—8528
[25]	Gaugg M. T., García-Gómez D., Collado C. B., de Miguel G. V., Kohler M., Zenobi R., J. Breath Res., 2016, 10, 016010
[26]	Phillips M., Herrera J., Krishnan S., Zain M., Greenberg J., Cataneo R. N., J. Chromatogr. B, 1999, 729, 75—88
[27]	Poli D., Carbognani P., Corradi M., Goldoni M., Acampa O., Balbi B., Bianchi L., Rusca M., Mutti A., Respir. Res., 2005, 6, 1—10