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Wang N, Xiao W, Tang Q, Hu W, Wang S, Zhang Z, Huang F. Plasma nicotine and its metabolite as biomarkers of tobacco exposure and their relevance to pulmonary nodule. Biomark Med 2024; 18:1061-1073. [PMID: 39564794 PMCID: PMC11633419 DOI: 10.1080/17520363.2024.2422809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 10/25/2024] [Indexed: 11/21/2024] Open
Abstract
Aim: Explore the optimal cut-off values for plasma nicotine and its metabolites in assessing smoking status and quantify the association between individual tobacco exposure and pulmonary nodules (PNs).Materials & methods: A total of 2245 plasma samples were included for the determination of nicotine (Nic), cotinine (Cot) and trans-3'-hydroxycotinine (OHCot) concentrations. The receiver operating characteristic curve was used to determine the optimal biomarkers reflecting smoking status. Binary logistic regression, restricted cubic spline and generalized linear model were used to analyze the association of nicotine and its metabolites with PNs. Quantile g-computation was used to investigate the mixed effects between them.Results: Cot was found to be the best biomarker of self-reported active-passive smoking, with optimal thresholds of 9.06 and 1.26 ng/ml, respectively. Except for OHCot, increased concentrations of Cot, Nic, total nicotine equivalent (TNE2) and TNE3 were significantly positively associated with the risk of PNs, whereas nicotine metabolite ratio presented a negative association. The mixed effects of OHCot, Cot and Nic were associated with PNs, with an odds ratio of 1.17 and a 95% CI of 1.05-1.30.Conclusion: Nicotine and its metabolites as potential biomarkers of tobacco exposure were significantly associated with PNs.
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Affiliation(s)
- Na Wang
- Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan Districts, Hefei, Anhui, 230032, China
| | - Wei Xiao
- Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan Districts, Hefei, Anhui, 230032, China
| | - Qian Tang
- Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan Districts, Hefei, Anhui, 230032, China
| | - Wenlei Hu
- Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan Districts, Hefei, Anhui, 230032, China
| | - Sheng Wang
- The Center for Scientific Research of Anhui Medical University, Hefei, Anhui, 230032, China
| | - Zhihua Zhang
- Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan Districts, Hefei, Anhui, 230032, China
| | - Fen Huang
- Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan Districts, Hefei, Anhui, 230032, China
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Szumska M, Mroczek P, Tyrpień-Golder K, Pastuszka B, Janoszka B. Determination of Cotinine, 3'-Hydroxycotinine and Nicotine 1'-Oxide in Urine of Passive and Active Young Smokers by LC-Orbitrap-MS/MS Technique. Molecules 2024; 29:3643. [PMID: 39125048 PMCID: PMC11313786 DOI: 10.3390/molecules29153643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024] Open
Abstract
Tobacco smoke is probably the most significant factor conducing to toxic xenobiotics exposure to humans. The aim of the study was to develop a rapid and sensitive method for the determination of selected nicotine metabolites in urine of tobacco smokers and passive smokers. The method for removing protein and extracting the metabolites involved the centrifugation of urine with acetonitrile. Cotinine, trans-3'-hydroxycotinine, and (2'S)-nicotine 1'-oxide in the supernatant were determined using the LC-Orbitrap-MS/MS technique, with the selected ion monitoring (SIM) and parallel reaction monitoring (PRM) modes used. The recovery of these analytes added to the urine samples ranged from 72% to 101%. Repeatability and reproducibility were less than 3.1% and 10.1%, respectively. The study was carried out among medical students. The group was selected as representatives of young people and who as future physicians should be more aware of the effects of nicotine use. Concentration levels of cotinine and trans-3'-hydroxycotinine determined in ng/mL in the urine of cigarette smokers were 70- and 58-fold higher, respectively, compared to passive smokers. Higher concentrations were recorded in the urine of those passively exposed to tobacco smoke than in non-smokers, confirming that passive exposure to tobacco smoke is not harmless to the human body. However, no significant differences were observed in the concentration of (1'S,2'S)-nicotine 1'-oxide in the samples of individuals from various groups.
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Affiliation(s)
- Magdalena Szumska
- Department of Chemistry, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland; (P.M.); (K.T.-G.)
- Research and Implementation Center Silesia LabMed, Medical University of Silesia, 40-752 Katowice, Poland;
| | - Paweł Mroczek
- Department of Chemistry, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland; (P.M.); (K.T.-G.)
| | - Krystyna Tyrpień-Golder
- Department of Chemistry, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland; (P.M.); (K.T.-G.)
| | - Beata Pastuszka
- Research and Implementation Center Silesia LabMed, Medical University of Silesia, 40-752 Katowice, Poland;
| | - Beata Janoszka
- Department of Chemistry, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland; (P.M.); (K.T.-G.)
- Research and Implementation Center Silesia LabMed, Medical University of Silesia, 40-752 Katowice, Poland;
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Gallart-Mateu D, Dualde P, Coscollà C, Soriano JM, Garrigues S, de la Guardia M. Biomarkers of exposure in urine of active smokers, non-smokers, and vapers. Anal Bioanal Chem 2023; 415:6677-6688. [PMID: 37743413 PMCID: PMC10598069 DOI: 10.1007/s00216-023-04943-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/05/2023] [Accepted: 09/06/2023] [Indexed: 09/26/2023]
Abstract
The exposure to smoking related products has been evaluated through urine illness risk marker determination through the analysis of urine samples of smokers and vapers. Biomarkers and their metabolites such as N-acetyl-S-(2-cyanoethyl)-L-cysteine (CEMA), N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-acetyl-S-[1-(hydroxymethyl)-2-propen-1-yl)-L-cysteine (MHBMA), N-acetyl-S-(3-hydroxypropyl)-L-cysteine (3HPMA), 2R-N-acetyl-S-(4-hydroxybutan-2-yl)-L-cysteine (HMPMA), and N-acetyl-S-(3-carboxy-2-propyl)-L-cysteine (CMEMA) together with nicotine and cotinine were identified and quantified by LC-HRMS and LC-MS/MS, and data found normalized to the creatinine level. One hundred two urine samples were collected from smokers, non-smokers, and vapers, spanning an age range from 16 to 79 years. Results obtained showed that CEMA was only detected in urine samples from smokers and MHBMA was in the same order of magnitude in all the urine samples analyzed. HMPMA was found in the urine of vapers at the same order of concentration as in non-smokers. 3HPMA in vapers was lower than in the urine of smokers, presenting an intermediate situation between smokers and non-smokers. On the other hand, DHBMA in vapers can reach similar values to those found for smokers, while CMEMA shows concentrations in the urine of vapers higher than in the case of non-smokers and traditional smokers, requiring new research to link this metabolite to the use of electronic cigarettes and possible alternative metabolomic routes. In general, this study seems to verify that traditional smoking practice constitutes a major source of carcinogenic chemicals compared with substitutive practices, although those practices are not free of potential harm.
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Affiliation(s)
- D Gallart-Mateu
- Department of Analytical Chemistry, University of Valencia, Research Building, 50 Dr. Moliner Street, 16100-Burjassot, Valencia, Spain
| | - P Dualde
- Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, Av. Catalunya, 21, 46020, Valencia, Spain
| | - C Coscollà
- Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, Av. Catalunya, 21, 46020, Valencia, Spain
| | - J M Soriano
- GISP Grup d'Investigació en Salut Pública, Universitat Politècnica de Catalunya, Barcelona, Spain
| | - S Garrigues
- Department of Analytical Chemistry, University of Valencia, Research Building, 50 Dr. Moliner Street, 16100-Burjassot, Valencia, Spain
| | - M de la Guardia
- Department of Analytical Chemistry, University of Valencia, Research Building, 50 Dr. Moliner Street, 16100-Burjassot, Valencia, Spain.
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Shields PG. Role of untargeted omics biomarkers of exposure and effect for tobacco research. ADDICTION NEUROSCIENCE 2023; 7:100098. [PMID: 37396411 PMCID: PMC10310069 DOI: 10.1016/j.addicn.2023.100098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Abstract
Tobacco research remains a clear priority to improve individual and population health, and has recently become more complex with emerging combustible and noncombustible tobacco products. The use of omics methods in prevention and cessation studies are intended to identify new biomarkers for risk, compared risks related to other products and never use, and compliance for cessation and reinitation. to assess the relative effects of tobacco products to each other. They are important for the prediction of reinitiation of tobacco use and relapse prevention. In the research setting, both technical and clinical validation is required, which presents a number of complexities in the omics methodologies from biospecimen collection and sample preparation to data collection and analysis. When the results identify differences in omics features, networks or pathways, it is unclear if the results are toxic effects, a healthy response to a toxic exposure or neither. The use of surrogate biospecimens (e.g., urine, blood, sputum or nasal) may or may not reflect target organs such as the lung or bladder. This review describes the approaches for the use of omics in tobacco research and provides examples of prior studies, along with the strengths and limitations of the various methods. To date, there is little consistency in results, likely due to small number of studies, limitations in study size, the variability in the analytic platforms and bioinformatic pipelines, differences in biospecimen collection and/or human subject study design. Given the demonstrated value for the use of omics in clinical medicine, it is anticipated that the use in tobacco research will be similarly productive.
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Affiliation(s)
- Peter G. Shields
- Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, Columbus, OH
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Qronfla MM, Jamoussi B, Chakroun R, Al-Mur BA, Halawani RF, Aloufi FA. Synthesis of a New Molecularly Imprinted Polymer and Optimisation of Phenylglyoxylic Acid Extraction from Human Urine Samples Using a Central Composite Design within the Response Surface Methodology. Polymers (Basel) 2023; 15:3279. [PMID: 37571173 PMCID: PMC10422317 DOI: 10.3390/polym15153279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 07/27/2023] [Accepted: 08/01/2023] [Indexed: 08/13/2023] Open
Abstract
Styrene, a chemical widely used in various industries, undergoes metabolic breakdown in the human body, resulting in the production of phenylglyoxylic acid (PGA). A novel molecularly imprinted polymer (MIP) was synthesised for selective extraction and enrichment of PGA in urine samples prior to high-performance liquid chromatography. The MIP employed in this research was a 4-vinylpyridine molecularly imprinted polymer (4-VPMIP) prepared via mass polymerisation using a noncovalent method. The structural and morphological characteristics of the molecularly imprinted polymers (MIPs) and non-imprinted polymers (NIPs) were evaluated using Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The efficiency of the molecularly imprinted solid-phase extraction (MISPE) process was optimised by investigating critical variables such as sample pH, sorbent mass, sample flow rate, and volume of the elution solvent. A central composite design (CCD) within the response surface methodology was utilised to develop separate models for the adsorption and desorption steps. Analysis of variance (ANOVA) confirmed the excellent fit of the experimental data to the proposed response models. Under the optimised conditions, the molecularly imprinted polymers exhibited a higher degree of selectivity and affinity for PGA, with a relative selectivity coefficient (α) of 2.79 against hippuric acid. The limits of detection (LOD) and quantification (LOQ) for PGA were determined to be 0.5 mg/L and 1.6 mg/L, respectively. The recoveries of PGA ranged from 97.32% to 99.06%, with a relative standard deviation (RSD) lower than 4.6%. Furthermore, MIP(4VP)SPE demonstrated the potential for recycling up to three times without significant loss in analyte recovery.
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Affiliation(s)
| | - Bassem Jamoussi
- Department of Environment, Faculty of Environmental Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.M.Q.); (R.C.); (B.A.A.-M.); (R.F.H.); (F.A.A.)
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Qronfla MM, Jamoussi B, Chakroun R. Synthesis and Characterization of a New Molecularly Imprinted Polymer for Selective Extraction of Mandelic Acid Metabolite from Human Urine as a Biomarker of Environmental and Occupational Exposures to Styrene. Polymers (Basel) 2023; 15:polym15102398. [PMID: 37242973 DOI: 10.3390/polym15102398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 05/17/2023] [Accepted: 05/19/2023] [Indexed: 05/28/2023] Open
Abstract
4-Vinylpyridine molecularly imprinted polymer (4-VPMIP) microparticles for mandelic acid (MA) metabolite as a major biomarker of exposure to styrene (S) were synthesized by bulk polymerization with a noncovalent approach. A common mole ratio of 1:4:20 (i.e., metabolite template: functional monomer: cross-linking agent, respectively) was applied to allow the selective solid-phase extraction of MA in a urine sample followed by high-performance liquid chromatography-diode array detection (HPLC-DAD). In this research, the 4-VPMIP components were carefully selected: MA was used as a template (T), 4-Vinylpyridine (4-VP) as a functional monomer (FM), ethylene glycol dimethacrylate (EGDMA) as a cross-linker (XL), and azobisisobutyronitrile (AIBN) as an initiator (I) and acetonitrile (ACN) as a porogenic solvent. Non-imprinted polymer (NIP) which serves as a "control" was also synthesized simultaneously under the same condition without the addition of MA molecules. Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) were used to characterize the imprinted and nonimprinted polymer to explain the structural and morphological characteristics of the 4-VPMIP and surface NIP. The results obtained from SEM depicted that the polymers were irregularly shaped microparticles. Moreover, MIPs surfaces had cavities and were rougher than NIP. In addition, all particle sizes were less than 40 µm in diameter. The IR spectra of 4-VPMIPs before washing MA were a little different from NIP, while 4-VPMIP after elution had a spectrum that was almost identical to the NIP spectrum. The adsorption kinetics, isotherms, competitive adsorption, and reusability of 4-VPMIP were investigated. 4-VPMIP showed good recognition selectivity as well as enrichment and separation abilities for MA in the extract of human urine with satisfactory recoveries. The results obtained in this research imply that 4-VPMIP might be used as a sorbent for MA solid-phase extraction (MISPE), for the exclusive extraction of MA in human urine.
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Affiliation(s)
- Murad M Qronfla
- Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Bassem Jamoussi
- Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Radhouane Chakroun
- Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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Abstract
This perspective summarizes available evidence on biomarkers of exposure in electronic nicotine delivery system (ENDS) users to aid the overall assessment of the health consequences of using ENDS. Identification of novel biomarkers of exposure specific to ENDS use remains challenging because chemicals emitted from ENDS devices have many familiar sources. The biomarker levels of many tobacco-related toxicants measured in biological samples collected from ENDS users did not differ significantly from non-users, except for nicotine metabolites and a small number of biomarkers of exposure to volatile organic compounds and tobacco-specific tobacco nitrosamines. Several studies have shown that while exposed to nicotine, long-term exclusive ENDS users showed significantly lower levels of toxicant biomarkers than cigarette smokers. Studies have also shown that concurrent users of ENDS and combustible cigarettes ('dual users') are not reducing overall exposure to harmful toxicants compared to exclusive cigarette smokers. Because of an absence of validated ENDS-specific biomarkers, we recommend combining several biomarkers to differentiate tobacco product user groups in population-based studies and monitor ENDS compliance in randomized controlled trials. Using a panel of biomarkers would provide a better understanding of health effects related to ENDS use.
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Affiliation(s)
- Maciej L Goniewicz
- Department of Health Behavior, Roswell Park Comprehensive Cancer Center, Elam and Carlton Streets, Buffalo NY 14226, United States
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Morgan AL, Torpy FR, Irga PJ, Fleck R, Gill RL, Pettit T. The botanical biofiltration of volatile organic compounds and particulate matter derived from cigarette smoke. CHEMOSPHERE 2022; 295:133942. [PMID: 35150705 DOI: 10.1016/j.chemosphere.2022.133942] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 02/06/2022] [Accepted: 02/08/2022] [Indexed: 06/14/2023]
Abstract
Despite the growing use of control measures, environmental tobacco smoke (ETS) remains a significant pollutant source in indoor air in many areas of the world. Current control methods for reducing ETS exposure are inadequate to protect public health in environments where cigarettes are smoked. An alternative solution is botanical biofiltration which has previously been shown to lower concentrations of volatile organic compounds (VOCs) and particulate matter (PM) from a range of polluted air streams. This study is the first to assess the potential of a botanical biofilter with the species Spathiphyllum wallisii (Peace Lily) for the removal of cigarette-derived VOCs and all size fractions of PM. Single pass removal efficiencies of 43.26% for total VOCs and 34.37% for total suspended particles were achieved. The botanical biofilter reduced the concentrations of a range of harmful ETS chemicals including nicotine, limonene, and toluene. Evaluation of the re-emission of ETS constituents filtered by the botanical biofilter revealed no particle resuspension or off gassing. The results demonstrate the potential of botanical biofilters to reduce public ETS exposure, although further research is needed to improve upon and ensure the efficiency of these systems for practical applications.
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Affiliation(s)
- Angela L Morgan
- Plants and Environmental Quality Research Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Australia; Environment and Planning, Aurecon, Australia
| | - Fraser R Torpy
- Plants and Environmental Quality Research Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Australia
| | - Peter J Irga
- Plants and Environmental Quality Research Group, School of Civil and Environmental Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Australia
| | - Robert Fleck
- Plants and Environmental Quality Research Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Australia
| | - Raissa L Gill
- Coastal Oceanography and Algal Research Team, Climate Change Cluster, Faculty of Science, University of Technology Sydney, Australia
| | - Thomas Pettit
- Plants and Environmental Quality Research Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Australia.
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Jin S, Pang W, Zhao L, Zhao Z, Mei S. Review of HPLC-MS methods for the analysis of nicotine and its active metabolite cotinine in various biological matrices. Biomed Chromatogr 2022; 36:e5351. [PMID: 35106788 DOI: 10.1002/bmc.5351] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 11/23/2021] [Accepted: 12/20/2021] [Indexed: 11/11/2022]
Abstract
In recent years, tobacco smoking is a risk factor for a series of diseases including cardiovascular diseases, cerebrovascular diseases, and cancers. Nicotine, the primary component of tobacco smoke, is mainly transformed to its active metabolite cotinine, which is often used as biomarker for tobacco exposure for its higher blood concentration and longer residence time than nicotine. Various analytical methods have been developed for the determination of nicotine and cotinine in biological matrices. This article reviewed the HPLC-MS based methods for nicotine and/or cotinine analysis in various biological matrices. The sample preparation, mass and chromatographic conditions and method validation results of these methods have been summarized and analyzed. Sample was mainly pretreated by protein precipitation and/or extraction. Separation was achieved using methanol and/or acetonitrile:water (with or without ammonium acetate) on C18 columns, and acetonitrile:water (with formic acid, ammonium acetate/formate) on HILIC columns. Nicotine-d3, nicotine-d4 and cotinine-d3 were commonly used internal standards. Other non-deuterated IS were also used such as ritonavir, N-ethylnorcotinine, and milrinone. For both nicotine and cotinine, the calibration range was 0.005-35000 ng/mL, the matrix effect was 75.96% - 126.8% and the recovery was 53% - 124.5%. The two analytes were stable at room temperature for 1-10 days, at -80 °C for up to 6 months, and after 3-6 freeze-thaw cycles. Comedications did not affect nicotine and cotinine analysis.
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Affiliation(s)
- Siyao Jin
- Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, P. R. China.,Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, P. R. China
| | - Wenyuan Pang
- Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, P. R. China.,Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China
| | - Libo Zhao
- Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, P. R. China.,Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, P. R. China
| | - Zhigang Zhao
- Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, P. R. China
| | - Shenghui Mei
- Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, P. R. China
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Yang J, Hashemi S, Han W, Lee C, Song Y, Lim Y. Study on the daily Ad Libitum smoking habits of active Korean smokers and their effect on urinary smoking exposure and impact biomarkers. Biomarkers 2021; 26:691-702. [PMID: 34530669 DOI: 10.1080/1354750x.2021.1981448] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Understanding interactions of smoking topography with biomarkers of exposure to tobacco is essential for accurate smoking risk assessments. METHODS In this study, the smoking topography and the levels of tobacco smoke exposure urinary biomarkers of a sample of active Korean smokers were quantified and measured. The results were used to investigate the effect of daily activities and smoking time on the smoking topography. Moreover, correlations between the smoking topography parameters and biomarkers were assessed. RESULTS No significant effect of either the daily activities or time on the smoking topography of the subjects were observed. Synchronic correlations of the cigarette consumption per day (CPD) and the average flow per puff with both urinary cotinine and trans-3'-hydroxycotinine were significant. For the urinary nicotine metabolites, the peak levels appeared when the CPD was over 19 cigarettes per day and the average puff velocity was between 35 and 45 ml/s. Nevertheless, when the average flow was over 60 ml/s, the levels of cotinine and trans-3'-hydroxycotinine significantly dropped. CONCLUSIONS The findings of this study may be beneficial for further smoking risk assessments with contributions of both the smoking topography and biomarkers to provide current smokers with applicable cession programs.Clinical significanceSmoking habits and levels of urinary biomarkers of Korean smokers are investigated.People with a higher dependency on nicotine smoke cigarettes with slower puffs.Effects of daily activities or time on smoking topography were not significant.Correlations between smoking topography and urinary biomarkers were significant.Peak biomarker levels were observed under certain smoking topography conditions.
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Affiliation(s)
- Jiyeon Yang
- Institute for Environmental Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Shervin Hashemi
- Institute for Environmental Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Wonseok Han
- Institute for Environmental Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chaelin Lee
- Graduate School of Public Health, Yonsei University, Seoul, Republic of Korea
| | - Yoojin Song
- Institute for Environmental Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Youngwook Lim
- Institute for Environmental Research, Yonsei University College of Medicine, Seoul, Republic of Korea
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Cohen G, Goldenson NI, Bailey PC, Chan S, Shiffman S. Changes in Biomarkers of Cigarette Smoke Exposure After 6 Days of Switching Exclusively or Partially to Use of the JUUL System with Two Nicotine Concentrations: A Randomized Controlled Confinement Study in Adult Smokers. Nicotine Tob Res 2021; 23:2153-2161. [PMID: 34161586 PMCID: PMC8570669 DOI: 10.1093/ntr/ntab134] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 06/21/2021] [Indexed: 02/07/2023]
Abstract
Introduction Evidence suggests that cigarette smokers who switch to electronic nicotine delivery systems (ENDS) reduce their exposure to harmful toxicants and carcinogens. It is unclear if dual-use is associated with decreases in exposure to toxicants. Methods This parallel-group confinement study assessed changes in biomarkers of exposure (BOEs) over six days among healthy adult smokers who were randomized into 1 of 11 study groups: eight JUUL-brand System (JUUL) groups (4 JUUL flavors [Virginia Tobacco, Menthol, Mint, Mango] × 2 nicotine concentrations [5.0% or 3.0% by weight]); Dual-Use group used preferred JUUL flavor (5.0% nicotine) and ≤50% usual brand (UB) cigarettes/day; UB Cigarette group and one group abstained from all tobacco/nicotine product use (Abstinence group). Urine and blood analysis assessed changes in primary BOE endpoints (NNAL, 3-HPMA, MHBMA, S-PMA COHb) and secondary BOE endpoints (NNN, HMPMA, CEMA, 1-OHP, O-toluidine, 2-NA, 4-ABP) among 279 adult smokers. Results In JUUL groups, median percent reductions in primary BOEs (Day 6–Baseline) were 90%–≥100% of Abstinence; there were no significant differences between JUUL groups and Abstinence. All reductions in JUUL groups were substantially and statistically significantly greater than reductions in the UB Cigarette group (ps < 0.025). Median reductions in primary BOEs in the Dual-Use group were 43%–55% of Abstinence. Similar results were observed for secondary BOEs. Conclusion This study suggests that the use of JUUL as a complete or partial substitute (i.e., dual-use with ≥50% reduction in cigarette consumption) for combustible cigarettes can substantially reduce exposure to multiple toxins associated with cigarette smoking. Implications This study adds to the growing body of evidence supporting the utility of ENDS products as potentially reduced-harm alternatives to cigarettes for adult smokers. Adult smokers who switched completely from cigarette smoking to use of the JUUL System (“JUUL”) in two nicotine concentrations (5.0% and 3.0%) and four flavors significantly reduced their exposure to multiple classes of cigarette-related toxicants. Additionally, smokers who used JUUL and continued smoking but reduced their daily cigarette consumption by ≥50% (dual users) also significantly reduced their toxicant exposure compared to cigarette smoking.
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Affiliation(s)
- Gal Cohen
- Juul Labs, Inc., Washington, DC, USA
- Corresponding Author: Gal Cohen, PhD, Juul Labs, Inc., 1000 F Street NW, Suite 800, Washington, D.C, 20004, USA. E-mail:
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Sibul F, Burkhardt T, Kachhadia A, Pilz F, Scherer G, Scherer M, Pluym N. Identification of biomarkers specific to five different nicotine product user groups: Study protocol of a controlled clinical trial. Contemp Clin Trials Commun 2021; 22:100794. [PMID: 34189337 PMCID: PMC8219643 DOI: 10.1016/j.conctc.2021.100794] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 02/09/2021] [Accepted: 05/23/2021] [Indexed: 01/03/2023] Open
Abstract
Background Assessing biomarker profiles in various body fluids is of large value to discern between the sole use of nicotine products. In particular, the assessment of the product compliance is required for long-term clinical studies. The objective of this study was the identification of biomarkers and biomarker patterns in body fluids, to distinguish between combustibles, heated tobacco products, electronic cigarettes, oral tobacco and oral/dermal nicotine products used for nicotine replacement therapy (NRT), as well as a control group of non-users. Methods A controlled, single-center study was conducted with 60 healthy subjects, divided into 6 groups (5 nicotine product user groups and one non-user group) based on their sole use of the products of choice. The subjects were confined for 76 h, during which, free and uncontrolled use of the products was provided. Sample collections were performed according to the study time schedule provided in Table 2. The primary outcome will be validated through analysis of the collected biospecimens (urine, blood, saliva, exhaled breath and exhaled breath condensate) by means of untargeted omics approaches (i.e. exposomics, breathomics and adductomics). Secondary outcome will include established biomarker quantification methods to allow for the identification of typical biomarker patterns. Statistical analysis tools will be used to specifically discriminate different product use categories. Results/Conclusions The clinical trial was successfully completed in May 2020, resulting in sample management and preparations for the quantitative and qualitative analyses. This work will serve as a solid basis to discern between biomarker profiles of different nicotine product user groups. The knowledge collected during this research will be required to develop prototype diagnostic tools that can reliably assess the differences and evaluate possible health risks of various nicotine products.
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Affiliation(s)
- Filip Sibul
- Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstr. 5, 82152 Planegg, Germany
| | - Therese Burkhardt
- Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstr. 5, 82152 Planegg, Germany
| | - Alpeshkumar Kachhadia
- Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstr. 5, 82152 Planegg, Germany
| | - Fabian Pilz
- Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstr. 5, 82152 Planegg, Germany
| | - Gerhard Scherer
- Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstr. 5, 82152 Planegg, Germany
| | - Max Scherer
- Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstr. 5, 82152 Planegg, Germany
| | - Nikola Pluym
- Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstr. 5, 82152 Planegg, Germany
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Habibagahi A, Siddique S, Harris SA, Alderman N, Aranda-Rodriguez R, Farhat I, Chevrier J, Kubwabo C. Challenges associated with quantification of selected urinary biomarkers of exposure to tobacco products. J Chromatogr B Analyt Technol Biomed Life Sci 2021; 1162:122490. [PMID: 33360416 DOI: 10.1016/j.jchromb.2020.122490] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 12/02/2020] [Accepted: 12/03/2020] [Indexed: 11/28/2022]
Abstract
Tobacco use, of which cigarette smoking is the most common, is a global health concern and is directly linked to over 7 million premature deaths annually. Measurement of the levels of tobacco-related biomarkers in biological matrices reflects human exposure to the chemicals in tobacco products. Nicotine, nicotine metabolites, anatabine, and anabasine are specific to tobacco and nicotine containing products. However, as nicotine and its metabolites are ubiquitous in the environment, background contamination during sample preparation can occur, making the quantification of target analytes challenging. The main purpose of the present study was to examine quality control measures needed in the determination of urinary nicotine, nicotine metabolites, anatabine, and anabasine. Urine samples (n = 75) and NIST standard reference materials SRM 3671 and SRM 3672 were analysed. A one-step extraction procedure using cold acetone was used in this study, which involved no additional clean up. The blank matrices investigated included synthetic urine prepared with HPLC-grade water, synthetic urine prepared with Milli-Q water, and bovine urine. By adopting strategies for minimizing the background levels, very low detection limits for all the target analytes ranging from 0.025 ng/mL for 3-hydroxycotinine to 0.634 ng/mL for nicotine, were achieved. Recoveries ranged between 67% and 118% with RSD values below 20%. Intra-day and inter-day precisions were in the range of 1.1-11.7% and 4.8-25.2%, respectively. The levels of all target analytes were higher in daily smokers than in non-smokers, with the largest difference observed for 3-hydroxycotinine. No difference was observed in the levels of target analytes between individuals who were former smokers, who never smoked or who were exposed to environmental tobacco smoke (ETS), except for total nicotine equivalents (TNE), which was significantly higher in non-smokers exposed to environmental tobacco smoke compared with study participants who never smoked. The results obtained from SRM 3671 and SRM 3672 could inform a potential certification of additional biomarkers of exposure to tobacco products in those standard reference materials.
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Affiliation(s)
- Arezoo Habibagahi
- Exposure and Biomonitoring Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada
| | - Shabana Siddique
- Exposure and Biomonitoring Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada
| | - Shelley A Harris
- Department of Epidemiology & Department of Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Nicholas Alderman
- Exposure and Biomonitoring Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada; Present address: Analysis and Air Quality Division, Environment and Climate Change Canada, Ottawa, ON, Canada
| | - Rocio Aranda-Rodriguez
- Exposure and Biomonitoring Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada
| | - Imen Farhat
- Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, QC, Canada
| | - Jonathan Chevrier
- Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, QC, Canada
| | - Cariton Kubwabo
- Exposure and Biomonitoring Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
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