scholarly journals A Sensitive LC–MS/MS Method for the Quantification of 3-Hydroxybenzo[a]pyrene in Urine-Exposure Assessment in Smokers and Users of Potentially Reduced-Risk Products

Separations ◽  
2021 ◽  
Vol 8 (10) ◽  
pp. 171
Author(s):  
Nadine Rögner ◽  
Heinz-Werner Hagedorn ◽  
Gerhard Scherer ◽  
Max Scherer ◽  
Nikola Pluym
Keyword(s):  
Spectrometry Method ◽  
Bioanalytical Method Validation ◽  
Limit Of Quantification ◽  
Cigarette Smokers ◽  
Biomarker Of Exposure ◽  
Human Carcinogen ◽  
The Us ◽  
Occupationally Exposed ◽  
Controlled Clinical Study ◽  
Reduced Risk

Benzo[a]pyrene (BaP), a human carcinogen, is formed during the incomplete combustion of organic matter such as tobacco. A suitable biomarker of exposure is the monohydroxylated metabolite 3-hydroxybenzo[a]pyrene (3-OH-BaP). We developed a sensitive LC–MS/MS (liquid chromatography coupled with tandem mass spectrometry) method for the quantification of urinary 3-OH-BaP. The method was validated according to the US Food and Drug Administration (FDA) guideline for bioanalytical method validation and showed excellent results in terms of accuracy, precision, and sensitivity (lower limit of quantification (LLOQ): 50 pg/L). The method was applied to urine samples derived from a controlled clinical study to compare exposure from cigarette smoking to the use of potentially reduced-risk products. Urinary 3-OH-BaP concentrations were significantly higher in smokers of conventional cigarettes (149 pg/24 h) compared to users of potentially reduced-risk products as well as non-users (99% < LLOQ in these groups). In conclusion, 3-OH-BaP is a suitable biomarker to assess the exposure to BaP in non-occupationally exposed populations and to distinguish not only cigarette smokers from non-smokers but also from users of potentially reduced-risk products.

scholarly journals Changes in Cigarettes per Day and Biomarkers of Exposure Among US Adult Smokers in the Population Assessment of Tobacco and Health Study Waves 1 and 2 (2013–2015)

2020 ◽  
Vol 22 (10) ◽  
pp. 1780-1787
Author(s):  
Brian L Rostron ◽  
Catherine G Corey ◽  
Joanne T Chang ◽  
Dana M van Bemmel ◽  
Mollie E Miller ◽  
...  
Keyword(s):  
Disease Risk ◽  
Smoking Status ◽  
Study Data ◽  
Health Study ◽  
Tobacco Exposure ◽  
Cigarette Smokers ◽  
Population Assessment ◽  
Biomarker Of Exposure ◽  
Biomarkers Of Exposure ◽  
The Us

Abstract Introduction Some studies have found some reduction in tobacco exposure and tobacco-related disease risk with decreased numbers of cigarettes smoked per day (CPD), but biomarker of exposure estimates by change in CPD are generally unavailable for the US population. Methods We analyzed biomarker of exposure data by smoking status from over 1100 adult exclusive daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study who were either exclusive daily smokers or had quit tobacco use entirely at Wave 2. Wave 1 smoking categories consisted of “very light” (1–4 CPD), “light” (5–9 CPD), “moderate” (10–19 CPD), and “heavy” (20+ CPD), and Wave 2 categories were “quitters” (stopped smoking entirely), exclusive cigarette “reducers” (CPD decreased ≥ 50%), “maintainers” (CPD within 50%–150% of Wave 1 value), and “increasers” (CPD increased ≥ 50%). Results Complete quitters had significantly lower levels of TNE-2, NNAL, NNN, 2-Fluorene, HPMA, CYMA, and MHB3 at Wave 2 for all Wave 1 CPD categories, and decreases were often large. Moderate “reducers” had lower levels of NNAL and 1-Hydroxypyrene at Wave 2, and heavy “reducers” had lower levels of NNAL, 2-Fluorene, and MHB3. Light “increasers” had higher levels of TNE-2, NNAL, 2-Fluorene, CYMA, and cadmium at Wave 2, and heavy “increasers” had higher levels of NNAL and HPMA. Conclusions Smoking “reducers” and “increasers” had changes in some biomarker of tobacco exposure levels, but reductions were much greater and more consistent for complete quitters. Implications PATH longitudinal cohort study data show that some exclusive daily cigarette smokers increase or decrease CPD over time. These differences may result in moderate changes in the levels of some biomarkers such as NNAL. Even so, however, reductions in biomarker levels are much greater with complete smoking cessation.

A STUDY OF A DOSE CONSTRAINT FOR OCCUPATIONALLY EXPOSED WORKERS IN THE US NUCLEAR POWER PLANTS

2018 ◽  
Vol 183 (4) ◽  
pp. 503-513 ◽  
Author(s):  
Tae Young Kong ◽  
Gamal Akabani ◽  
John W Poston
Keyword(s):  
Nuclear Power ◽  
Power Plants ◽  
Nuclear Power Plants ◽  
Radiological Protection ◽  
Occupational Dose ◽  
The Us ◽  
Exposed Workers ◽  
Occupationally Exposed ◽  
Dose Constraint ◽  
Dose Constraints

Abstract One of the most important issues in the nuclear power industry is the implementation of the 2007 Recommendations of the International Commission on Radiological Protection (ICRP) published in ICRP Publication 103. These recommendations include the implementation of the concept of dose constraints for occupationally exposed workers at nuclear power plants (NPPs). When considering these changes from a cost–benefit standpoint, the implementation of dose constraints is still highly controversial. This study analysed annual occupational dose distributions to determine whether a dose constraint is needed for occupationally exposed workers at the US NPPs. Results of the analysis showed that the use of dose constraints had no positive impact on radiation safety of workers at NPPs in the USA. In fact, it appears that the implementation of dose constraints will impose an unnecessary regulatory burden on licensees. Based on these results, implementation of dose constraints is not recommended.

scholarly journals Development of UHPLC-MS/MS Method for Indirubin-3′-Oxime Derivative as a Novel FLT3 Inhibitor and Pharmacokinetic Study in Rats

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2039
Author(s):  
Na Yoon Kim ◽  
Yong-Chul Kim ◽  
Yoon Gyoon Kim
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Reaction Monitoring ◽  
Spectrometry Method ◽  
Limit Of Quantification ◽  
Flt3 Inhibitor ◽  
Pharmacokinetic Properties ◽  
Safety Guidelines ◽  
The U.S

This study aimed to develop and validate a sensitive liquid chromatography-coupled tandem mass spectrometry method for the quantification of LDD-2614, an indirubin derivative and novel FLT3 inhibitor, in rat plasma. In addition, the developed analytical method was applied to observe the pharmacokinetic properties of LDD-2614. Chromatographic separation was achieved on a Luna omega C18 column using a mixture of water and acetonitrile, both containing 0.1% formic acid. Quantitation was performed using positive electrospray ionization in a multiple reaction monitoring (MRM) mode. The MRM transitions were optimized as m/z 426.2→113.1 for LDD-2614 and m/z 390.2→113.1 for LDD-2633 (internal standard), and the lower limit of quantification (LLOQ) for LDD-2614 was determined as 0.1 ng/mL. Including the LLOQ, the nine-point calibration curve was linear with a correlation coefficient greater than 0.9991. Inter- and intraday accuracies (RE) ranged from −3.19% to 8.72%, and the precision was within 9.02%. All validation results (accuracy, precision, matrix effect, recovery, stability, and dilution integrity) met the acceptance criteria of the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety guidelines. The proposed method was validated and demonstrated to be suitable for the quantification of LDD-2614 for pharmacokinetics studies.

The relationship between smoking machine derived tar yields and biomarkers of exposure in adult cigarette smokers in the US

2009 ◽  
Vol 55 (1) ◽  
pp. 17-27 ◽  
Author(s):  
Paul Mendes ◽  
Qiwei Liang ◽  
Kimberly Frost-Pineda ◽  
Sagar Munjal ◽  
Ruediger-A. Walk ◽  
...  
Keyword(s):  
Cigarette Smokers ◽  
Biomarkers Of Exposure ◽  
The Us ◽  
The Relationship

scholarly journals Urinary N7-(1-hydroxy-3-buten-2-yl) guanine adducts in humans: temporal stability and association with smoking

Mutagenesis ◽  
2019 ◽  
Vol 35 (1) ◽  
pp. 19-26
Author(s):  
Caitlin C Jokipii Krueger ◽  
Guru Madugundu ◽  
Amanda Degner ◽  
Yesha Patel ◽  
Daniel O Stram ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cigarette Smoke ◽  
Solid Phase ◽  
Smoking Status ◽  
Temporal Stability ◽  
Metabolic Activation ◽  
Human Carcinogen ◽  
Guanine Adducts ◽  
Occupationally Exposed ◽  
Covalent Adducts

Abstract 1,3-Butadiene (BD) is a known human carcinogen found in cigarette smoke, automobile exhaust, and urban air. Workers occupationally exposed to BD in the workplace have an increased incidence of leukemia and lymphoma. BD undergoes cytochrome P450-mediated metabolic activation to 3,4-epoxy-1-butene (EB), 1,2,3,4-diepoxybutane (DEB) and 1,2-dihydroxy-3,4-epoxybutane (EBD), which form covalent adducts with DNA. We have previously reported a quantitative nanoLC/ESI+-HRMS3 method for urinary N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts as a mechanism-based biomarker of BD exposure. In the present study, the method was updated to include high throughput 96-well solid phase extraction (SPE) and employed to establish urinary EB-GII biomarker stability and association with smoking. Urinary EB-GII levels were measured bimonthly for 1 year in 19 smokers to determine whether single adduct measurement provides reliable levels of EB-GII in an individual smoker. In addition, association of EB-GII with smoking was studied in 17 individuals participating in a smoking cessation program. EB-GII levels decreased 34% upon smoking cessation, indicating that it is associated with smoking status, but may also originate from sources other than exposure to cigarette smoke.

P032 E-CIGARETTE AND CIGARETTE USE AMONG U.S. ADULT IBD PATIENTS: POPULATION-LEVEL SURVEY

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S62-S63
Author(s):  
Ryan Suk ◽  
Heetae Suk ◽  
Kalyani Sonawane ◽  
Ashish Deshmukh
Keyword(s):  
Cigarette Smoking ◽  
Lung Injury ◽  
Survey Design ◽  
Population Level ◽  
Cigarette Use ◽  
Cigarette Smokers ◽  
The Us ◽  
Current Cigarette ◽  
Lung Injuries ◽  
Nationally Representative

Abstract Background Cigarette smoking can negatively affect treatment response in inflammatory bowel disease (IBD) patients, especially among those with Crohn’s disease (CD). E-cigarette has been considered a safer alternative to delivering nicotine for IBD patients who smoke. However, given the recent large number of reported e-cigarette-related lung injury cases, CDC released an interim guidance update on those lung injuries. They also coined a term EVALI (e-cigarette, or vaping, product use associated lung injury) emphasizing the possible harms in e-cigarette smoking. To the best our knowledge, we currently do not know the recent smoking habits in American IBD patients, especially when it reveals that e-cigarette use might cause serious lung injuries. Methods We used National Health Interview Survey (NHIS) for 2015–2016, which is a nationally representative survey for noninstitutionalized adults in the US. Weighted counts and percentages were estimated using survey design for the population-level results. We identified those who reportedly were told by a doctor or healthcare professional that they have IBD. We first estimated the prevalence of current e-cigarette or cigarette use among IBD patients. We then estimated the frequency of use (every day or some days) among the current users. We also categorized IBD patients into 4 groups by smoking type: those using e-cigarette only, cigarette only, using both, and neither. To see the characteristics of e-cigarette users, we stratified e-cigarette users by current/former/never cigarette use status. Results We identified 951 participants (population estimate: 3.1 million) with IBD. Among those people, 5.0% (95% CI: 3.1–6.9) was current e-cigarette users while 17.9% (95% CI: 14.8–21.0) was current cigarette smokers. Prevalence of every-day use and some-day use of e-cigarette was similar (2.4% vs 2.6%), while there was much higher prevalence of every-day use than some-day use in cigarette (15.3% vs 2.6%). Those who were using both e-cigarette and cigarette was 3.2% (Table). Majority of e-cigarette users were also currently using cigarette (63.6%, 95% CI: 48.9–78.3), while 32.7% (95% CI: 18.4–47.0) of them were former cigarette smokers. Only 3.7% (0.0–8.9) of them never used cigarettes. Conclusion While numerous studies show e-cigarette use is generally increasing rapidly in the US, we found that 5% of IBD patients are currently using e-cigarette. Almost two-thirds of them were also currently smoking cigarette and one-third of them were former smokers. It is possible that most of the e-cigarette users are still in the process of transitioning from cigarette smoking and thus using both types. We lack information on effects of using e-cigarette or both e-cigarette and cigarette in IBD treatment outcomes, as well as how e-cigarette use will complicate other health risks in IBD patients (e.g. lung injuries). We need further research on these effects to properly guide IBD patients who are in need of smoking cessation.

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