Abstract
Human beings are inevitably exposed to volatile organic compounds (VOCs) of anthropogenic emissions as they are ubiquitous atmospheric pollutants. Smoking is an important exposure route of VOCs for the general population. Health effects induced by VOC exposure raise more concerns as they are identified with carcinogenicity, genotoxicity, neurotoxicity, and reproductive toxicity. trans-3′-Hydroxycotinine (OH-Cot) is a urinary biomarker of smoking, and 8-hydroxy-2′-deoxyguanosine (8-OHDG) is a urinary biomarker of DNA oxidative damage. To develop a method for quantifying VOC exposure levels of the general population and assessing the health risks induced by VOCs from second-hand smoking, an effective, rapid, and high-throughput method for the simultaneous determination of 31 metabolites of VOCs, 8-OHDG, and OH-Cot using solid-phase extraction coupled with UPLC-MS/MS was developed and validated. Method precision and accuracy, extraction recoveries, matrix effects, and storage stabilities of most analytes met the criterion (80–120%). Extraction recoveries increased from 85.1 to 100% after adjustment by isotoped internal standards (ISs). Furthermore, 13C- and 15N-labeled ISs were more effective to reduce the influence of matrix effects on recoveries and precisions than the deuterated analogs (73.0–116% vs. 53.6–140%). This developed method was successfully applied to determine urine samples collected from children. Results showed that N-acetyl-S-(3,4-dihydrobutyl)-l-cysteine, 2,2′-thiodiacetic acid (TGA), and N-acetyl-S-(3-hydroxypropyl-1-methyl)-l-cysteine (HPMMA) were well correlated with 8-OHDG with coefficients higher than 0.82, indicating those VOCs might easily lead to DNA damage. In conclusion, our co-monitoring of metabolites of VOCs with 8-OHDG and OH-Cot in one method provides a robust analytical method, which not only suggests the potential adverse health effects induced by VOCs but also discriminates and evaluates the contribution of passive smoking in human VOC exposure.
Similar content being viewed by others
References
Chen J, Huang Y, Li G, An T, Hu Y, Li Y. VOCs elimination and health risk reduction in e-waste dismantling workshop using integrated techniques of electrostatic precipitation with advanced oxidation technologies. J Hazard Mater. 2016;302:395–403. https://doi.org/10.1016/j.jhazmat.2015.10.006.
Chen J, Zhang D, Li G, An T, Fu J. The health risk attenuation by simultaneous elimination of atmospheric VOCs and POPs from an e-waste dismantling workshop by an integrated de-dusting with decontamination technique. Chem Eng J. 2016;301:299–305. https://doi.org/10.1016/j.cej.2016.05.013.
Kumar A, Singh D, Kumar K, Singh BB, Jain VK. Distribution of VOCs in urban and rural atmospheres of subtropical India: temporal variation, source attribution, ratios, OFP and risk assessment. Sci Total Environ. 2018;613-614:492–501. https://doi.org/10.1016/j.scitotenv.2017.09.096.
Hadgsan AT, Daisey JM, Mahanama KRR, Ten Brinka J. Use of volatile tracers to determine the contribution of environmental tobacco smoke to concentrations of volatile organic compounds in smoking environments. Environ Int. 1996;22(3):295–307. https://doi.org/10.1016/0160-4120(96)00015-3.
Hong-Li W, Sheng-Ao J, Sheng-Rong L, Qing-Yao H, Li L, Shi-Kang T, et al. Volatile organic compounds (VOCs) source profiles of on-road vehicle emissions in China. Sci Total Environ. 2017;607-608:253–61. https://doi.org/10.1016/j.scitotenv.2017.07.001.
Wang H, Xiang Z, Wang L, Jing S, Lou S, Tao S, et al. Emissions of volatile organic compounds (VOCs) from cooking and their speciation: a case study for Shanghai with implications for China. Sci Total Environ. 2018;621:1300–9. https://doi.org/10.1016/j.scitotenv.2017.10.098.
Paci E, Pigini D, Caporossi L, De Rosa M, Santoro A, Sisto R, et al. Matrix effect in the quantitative determination of mandelic and phenylglyoxylic acid in urine samples by HPLC-MS/MS with isotopic dilution. Curr Anal Chem. 2013;9(3):439–46. https://doi.org/10.2174/1573411011309030013.
Agents classified by the IARC monographs, volumes 1–122.
Jackson MA, Stack HF, Rice JM, Waters MD. A review of the genetic and related effects of 1,3-butadiene in rodents and humans. Mutat Res. 2000;463(3):181–213. https://doi.org/10.1016/s1383-5742(00)00056-9.
Kerzic PJ, Irons RD. Distribution of chromosome breakpoints in benzene-exposed and unexposed AML patients. Environ Toxicol Pharmacol. 2017;55:212–6. https://doi.org/10.1016/j.etap.2017.08.033.
Talibov M, Sormunen J, Hansen J, Kjaerheim K, Martinsen JI, Sparen P, et al. Benzene exposure at workplace and risk of colorectal cancer in four Nordic countries. Cancer Epidemiol. 2018;55:156–61. https://doi.org/10.1016/j.canep.2018.06.011.
Zhang X, Hou H, Chen H, Liu Y, Wang A, Hu Q. A column-switching LC-MS/MS method for simultaneous quantification of biomarkers for 1,3-butadiene exposure and oxidative damage in human urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2015;1002:123–9. https://doi.org/10.1016/j.jchromb.2015.08.012.
An T, Huang Y, Li G, He Z, Chen J, Zhang C. Pollution profiles and health risk assessment of VOCs emitted during e-waste dismantling processes associated with different dismantling methods. Environ Int. 2014;73:186–94. https://doi.org/10.1016/j.envint.2014.07.019.
Jia C, Yu X, Masiak W. Blood/air distribution of volatile organic compounds (VOCs) in a nationally representative sample. Sci Total Environ. 2012;419:225–32. https://doi.org/10.1016/j.scitotenv.2011.12.055.
Li X, Guo Y, Song X, He Y, Zhang H, Bao H, et al. A cross-sectional survey based on blood VOCs, hematological parameters and urine indicators in a population in Jilin. Northeast China. Environ Geochem Health. 2019. https://doi.org/10.1007/s10653-019-00241-6.
Boettcher MI, Bolt HM, Drexler H, Angerer J. Excretion of mercapturic acids of acrylamide and glycidamide in human urine after single oral administration of deuterium-labelled acrylamide. Arch Toxicol. 2006;80(2):55–61. https://doi.org/10.1007/s00204-005-0011-y.
Ding YS, Blount BC, Valentin-Blasini L, Applewhite HS, Xia Y, Watson CH, et al. Simultaneous determination of six mercapturic acid metabolites of volatile organic compounds in human urine. Chem Res Toxicol. 2009;22(6):1018–25. https://doi.org/10.1021/tx800468w.
Zhang X, Xiong W, Shi L, Hou H, Hu Q. Simultaneous determination of five mercapturic acid derived from volatile organic compounds in human urine by LC-MS/MS and its application to relationship study. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;967:102–9. https://doi.org/10.1016/j.jchromb.2014.07.013.
Sabatini L, Barbieri A, Indiveri P, Mattioli S, Violante FS. Validation of an HPLC-MS/MS method for the simultaneous determination of phenylmercapturic acid, benzylmercapturic acid and o-methylbenzyl mercapturic acid in urine as biomarkers of exposure to benzene, toluene and xylenes. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;863(1):115–22. https://doi.org/10.1016/j.jchromb.2008.01.022.
Alwis KU, Blount BC, Britt AS, Patel D, Ashley DL. Simultaneous analysis of 28 urinary VOC metabolites using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS). Anal Chim Acta. 2012;750:152–60. https://doi.org/10.1016/j.aca.2012.04.009.
Kotapati S, Esades A, Matter B, Le C, Tretyakova N. High throughput HPLC-ESI(-)-MS/MS methodology for mercapturic acid metabolites of 1,3-butadiene: biomarkers of exposure and bioactivation. Chem Biol Interact. 2015;241:23–31. https://doi.org/10.1016/j.cbi.2015.02.009.
Hylckama Vlieg JETV. Reactive epoxides as intermediates in the bacterial metabolism of isoprene and chlorinated ethenes: University of Groningen; 1999.
Loft S, Fischer-Nielsen A, Jeding IB, Vistisen K, Poulsen HE. 8-Hydroxydeoxyguanosine as a urinary biomarker of oxidative DNA damage. J Toxicol Environ Health. 1993;40(2-3):391–404. https://doi.org/10.1080/15287399309531806.
Ren L, Fang J, Liu G, Zhang J, Zhu Z. Liu, Lin K, Zhang H, Lu S. Simultaneous determination of urinary parabens, bisphenol A, triclosan, and 8-hydroxy-2′-deoxyguanosine by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Anal Bioanal Chem. 2016;408(10):2621–9. https://doi.org/10.1007/s00216-016-9372-8.
Li J, Lu S, Liu G, Zhou Y, Lv Y, She J, et al. Co-exposure to polycyclic aromatic hydrocarbons, benzene and toluene and their dose-effects on oxidative stress damage in kindergarten-aged children in Guangzhou, China. Sci Total Environ. 2015;524-525:74–80. https://doi.org/10.1016/j.scitotenv.2015.04.020.
Li J, Fan R, Lu S, Zhang D, Zhou Y, Lv Y. Exposure to polycyclic aromatic hydrocarbons could cause their oxidative DNA damage: a case study for college students in Guangzhou. China. Environ Sci Pollut Res Int. 2015;22(3):1770–7. https://doi.org/10.1007/s11356-014-2769-z.
Fan R, Wang D, Mao C, Ou S, Lian Z, Huang S, et al. Preliminary study of children’s exposure to PAHs and its association with 8-hydroxy-2′-deoxyguanosine in Guangzhou. China. Environ Int. 2012;42:53–8. https://doi.org/10.1016/j.envint.2011.03.021.
Liu Y, Shao M, Fu L, Lu S, Zeng L, Tang D. Source profiles of volatile organic compounds (VOCs) measured in China: part I. Atmos Environ. 2008;42(25):6247–60. https://doi.org/10.1016/j.atmosenv.2008.01.070.
Piller M, Gilch G, Scherer G, Scherer M. Simple, fast and sensitive LC-MS/MS analysis for the simultaneous quantification of nicotine and 10 of its major metabolites. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;951-952:7–15. https://doi.org/10.1016/j.jchromb.2014.01.025.
Lopukhov LV, Laikov AV, Romanova VA, Gatina DZ, Lopukhov VL, Abdulkhakov SR, et al. LC-MS method development for simultaneous determination of trans-3′-hydroxycotinine and three mercapturic acids in urine. BioNanoScience. 2018;8(3):924–9. https://doi.org/10.1007/s12668-018-0528-1.
Fan R, Wang D, Ramage R, She J. Fast and simultaneous determination of urinary 8-hydroxy-2′-deoxyguanosine and ten monohydroxylated polycyclic aromatic hydrocarbons by liquid chromatography/tandem mass spectrometry. Chem Res Toxicol. 2012;25(2):491–9. https://doi.org/10.1021/tx200517h.
EMA. Guideline on bioanalytical method validation. EMEA/CHMP/EWP/192217/20092011.
Sundstrom I, Bondesson U, Hedeland M. Identification of phase I and phase II metabolites of ketobemidone in patient urine using liquid chromatography–electrospray tandem mass spectrometry. J Chromatogr B. 2001;763:121–31.
Fan R, Ramage R, Wang D, Zhou J, She J. Determination of ten monohydroxylated polycyclic aromatic hydrocarbons by liquid-liquid extraction and liquid chromatography/tandem mass spectrometry. Talanta. 2012;93:383–91. https://doi.org/10.1016/j.talanta.2012.02.059.
Mathias PI, B’Hymer C. A survey of liquid chromatographic-mass spectrometric analysis of mercapturic acid biomarkers in occupational and environmental exposure monitoring. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;964:136–45. https://doi.org/10.1016/j.jchromb.2014.02.057.
Bergh MS, Bogen IL, Lundanes E, Oiestad AML. Validated methods for determination of neurotransmitters and metabolites in rodent brain tissue and extracellular fluid by reversed phase UHPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2016;1028:120–9. https://doi.org/10.1016/j.jchromb.2016.06.011.
Fan R, Wang D, She J. Method development for the simultaneous analysis of trans,trans-muconic acid, 1,2-dihydroxybenzene, S-phenylmercapturic acid and S-benzylmercapturic acid in human urine by liquid chromatography/tandem mass spectrometry. Analytical Methods. 2015;7(2):573–80. https://doi.org/10.1039/c4ay02261k.
Suh JH, Eom HY, Kim U, Kim J, Cho HD, Kang W, et al. Highly sensitive electromembrane extraction for the determination of volatile organic compound metabolites in dried urine spot. J Chromatogr A. 2015;1416:1–9. https://doi.org/10.1016/j.chroma.2015.09.004.
Li G, Wang L, Fei T, Liu H, Wu D, Zheng S. Ionic liquid-based ultrasonic-assisted extraction combined with HPLC–MS/MS for the determination of seven mercapturic acids in human urine. Chromatographia. 2015;78:641–8. https://doi.org/10.1007/s10337-015-2878-y.
Hartmann EC, Boettcher MI, Schettgen T, Fromme H, Drexler H, Angerer J. Hemoglobin adducts and mercapturic acid excretion of acrylamide and glycidamide in one study population. J Agric Food Chem. 2008;56:6061–8.
Chiang WC, Chen CY, Lee TC, Lee HL, Lin YW. Fast and simple screening for the simultaneous analysis of seven metabolites derived from five volatile organic compounds in human urine using on-line solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry. Talanta. 2015;132:469–78. https://doi.org/10.1016/j.talanta.2014.09.029.
Marchi I, Rudaz S, Veuthey JL. Sample preparation development and matrix effects evaluation for multianalyte determination in urine. J Pharm Biomed Anal. 2009;49(2):459–67. https://doi.org/10.1016/j.jpba.2008.11.040.
Judak P, Van Eenoo P, Deventer K. Urinary matrix effects in electrospray ionization mass spectrometry in the presence of DMSO. J Mass Spectrom. 2018;53(10):1018–21. https://doi.org/10.1002/jms.4255.
Abe K, Suzuki H, Maekawa M, Shimada M, Yamaguchi H, Mano N. Matrix effect-corrected liquid chromatography/tandem mass-spectrometric method for determining acylcarnitines in human urine. Clin Chim Acta. 2017;468:187–94. https://doi.org/10.1016/j.cca.2017.03.001.
Matuszewski BK, Constanzer ML, Chavez-Eng CM. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem. 2003;75(13):3019–30. https://doi.org/10.1021/ac020361s.
Stokvis E, Rosing H, Beijnen JH. Stable isotopically labeled internal standards in quantitative bioanalysis using liquid chromatography/mass spectrometry: necessity or not? Rapid Commun Mass Spectrom. 2005;19(3):401–7. https://doi.org/10.1002/rcm.1790.
Conflict of interest
The authors declare that they have no conflict of interest.
Funding
This research was supported by grants from the National Natural Science Foundation of China (No. 41731279, No. 21477041, No. 21777048).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study was approved by the Research Ethics Committee of South China Normal University (No. 2017012). The parent or guardian of each participant signed an informed consent and was required to complete a questionnaire including gender, age, height, weight, lifestyle habits, and passive smoking frequency as well as the past medical history and genetics of their children before sampling.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary materials
ESM 1
(PDF 348 kb)
Rights and permissions
About this article
Cite this article
Kuang, H., Li, Y., Jiang, W. et al. Simultaneous determination of urinary 31 metabolites of VOCs, 8-hydroxy-2′-deoxyguanosine, and trans-3′-hydroxycotinine by UPLC-MS/MS: 13C- and 15N-labeled isotoped internal standards are more effective on reduction of matrix effect. Anal Bioanal Chem 411, 7841–7855 (2019). https://doi.org/10.1007/s00216-019-02202-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-019-02202-5