Simultaneous determination of tobacco minor alkaloids and tobacco‐specific nitrosamines in mainstream smoke by dispersive solid‐phase extraction coupled with ultra‐performance liquid chromatography/tandem orbitrap mass spectrometry

Zhang, Xiaotao; Wang, Ruoning; Zhang, Li; Ruan, Yi; Wang, Weiwei; Houwei, JI; Lin, Fu‐Cheng; Liu, Jian

doi:10.1002/rcm.8222

Cited by 13 publications

(4 citation statements)

References 33 publications

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“…Although myosmine and norharman peaks did not have MS/MS spectra in the switching experiment, they had RTs and m/z values that matched standard compound analyses. Myosmine is found in tobacco leaves (Benowitz et al, 2009;Zhang et al, 2018), whereas norharman is generated primarily from the combustion of tobacco (Zhang et al, 2011). In this study, 901 peaks out of 1,180 did not have MS/MS spectra; however, identification can be supported by these experimental contexts (Schymanski et al, 2014).…”

Section: Compound Identification and Deviation Of Peak Areasmentioning

confidence: 48%

“…For the three missing peaks in the switching study, a peak with an RT of 5.47 min and m/z ([M+H] + for all following values) of 149.1067 was possibly nornicotine according to the library search. Nornicotine is a metabolite of nicotine and generally found in CS (Zhang et al, 2018;Rodgman and Perfetti, 2013); however, nornicotine is not reproducibly detected in experiments using a standard compound because of the drying steps required for sample preparation (Mathon et al, 2019).…”

Section: Compound Identification and Deviation Of Peak Areasmentioning

confidence: 99%

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LC/MS analysis of three-dimensional model cells exposed to cigarette smoke or aerosol from a novel tobacco vapor product

2020

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A novel tobacco vapor product (NTV) contains tobacco leaves and generates nicotinecontaining aerosols using heating elements. Subchronic biological effects have been evaluated previously using three-dimensional bronchial epithelial model cells by repeated exposure to cigarette smoke (CS) and the NTV aerosols; however, the intracellular exposure characteristics have not been studied in detail. In this study, cells were initially exposed to an aqueous extract (AqE) of cigarette smoke (CS) at two concentration levels, and the cell lysate underwent untargeted analysis by LC-high resolution mass spectrometry to determine the exogenous compounds present in the cells. Among the thousands of peaks detected, four peaks showed a CS-dependency, which were reproducibly detected. Two of the peaks were nicotine and nicotine N-oxide, and the other two putative compounds were myosmine and norharman. The cells were then exposed to an AqE of CS in various combinations of exposure and post-exposure culture durations. Post-exposure culturing of cells with fresh medium markedly decreased the peak areas of the four compounds. The in-vitro switching study of CS to NTV aerosols was investigated by intermittently exposing cells to an AqE of CS four times, followed by exposure to either an AqE of CS, NTV aerosol or medium another four times. Switching to NTV reduced myosmine and norharman levels, which are known CS constituents. The results indicate that extracellular compounds inside cells reflect the exposure state outside cells. Thus, monitoring functional changes to cells in these exposure experiments is feasible.

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Section: Compound Identification and Deviation Of Peak Areasmentioning

confidence: 48%

Section: Compound Identification and Deviation Of Peak Areasmentioning

confidence: 99%

LC/MS analysis of three-dimensional model cells exposed to cigarette smoke or aerosol from a novel tobacco vapor product

2020

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“…The contents of some harmful substances in the CSE of denicotinized cigarettes were consistent with those found in 3R4F reference cigarettes ( Figure 1A ), except for lower concentrations of tobacco-specific nitrosamines [TSNA, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK; N′-nitrosonornicotine, NNN; N′-nitrosoanatabine, NAT and N-nitrosoanabasine, NAB]. This is the characteristic difference between Chinese Virginia cigarettes (mainly containing flue-cured tobacco) and 3R4F reference cigarettes (blended cigarettes) ( Xiong et al, 2010 ; Zhang et al, 2018 ) which is also the reason for the difference in minor alkaloids. To better understand the non-nicotine constituents in this study, the nicotine content of the cut tobacco in the experimental cigarettes was reduced to 0.7 mg/g, which was 2.8% of the 3R4F standard cigarette level ( Figure 1B ), and was close to 0.4–0.6 mg/g ( Bespalov et al, 1999 ; Rodgman and Perfetti, 2008 ; Piechota et al, 2010 ; Rose et al, 2010 ; Ashok et al, 2017 ) in other studies of denicotinized cigarettes.…”

Section: Discussionmentioning

confidence: 99%

Non-nicotine constituents in cigarette smoke extract enhance nicotine addiction through monoamine oxidase A inhibition

et al. 2022

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Tobacco addiction has been largely attributed to nicotine, a component in tobacco leaves and smoke. However, extensive evidence suggests that some non-nicotine components of smoke should not be overlooked when considering tobacco dependence. Yet, their individual effect and synergistic effect on nicotine reinforcement remain poorly understood. The study herein focused on the role of non-nicotine constituents in promoting the effects of nicotine and their independent reinforcing effects. Denicotinized cigarettes were prepared by chemical extracting of cut tobacco, and the cigarette smoke extracts (CSE, used as a proxy for non-nicotine ingredients) were obtained by machine-smoking the cigarettes and DMSO extraction. The compositions of harmful components, nicotine, and other minor alkaloids in both cut tobacco and the CSE of experimental denicotinized cigarettes were examined by GC-MS, and compared with 3R4F reference cigarettes. individually and in synergy with nicotine were determined by conditioned place preference (CPP), dopamine (DA) level detection, the open field test (OFT), and the elevated plus maze (EPM). Finally, the potential enhancement mechanism of non-nicotinic constituents was investigated by nicotine metabolism and monoamine oxidase A (MAOA) activity inhibition in the striatum of mice and human recombinant MAOA. Thenicotine content in smoke from the experimental denicotinized cigarettes (under ISO machine-smoking conditions) was reduced by 95.1% and retained most minor alkaloids, relative to the 3R4F reference cigarettes. It was found that non-nicotine constituents increased acute locomotor activities. This was especially pronounced for DA levels in NAc and CPP scores, decreased the time in center zone. There were no differences in these metrics with DNC group when compared to the NS group. Non-nicotine constituents alone did not show reinforcing effects in CPP or striatum DA levels in mice. However, in the presence of nicotine, non-nicotine constituents further increased the reinforcing effects. Furthermore, non-nicotine constituents may enhance nicotine’s reinforcing effects by inhibiting striatum MAOA activity rather than affecting nicotine metabolism or total striatum DA content in mice. These findings expand our knowledge of the effect on smoking reinforcement of non-nicotine constituents found in tobacco products.

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“…A highresolution accurate mass spectrometer capable of performing tandem mass spectrometry (MS/MS) is often required for nitrosamine analysis. While there are modern publications that focus on the determination of known nitrosamines that are commonly observed as contaminants or reaction byproducts from common nitrogencontaining solvents, [16][17][18][19][20] there is much less literature available regarding molecules containing some of the more common substructures seen in many small molecule pharmaceutical compounds. Additionally, a thorough understanding of the gas-phase fragmentation behavior of nitrosamines is needed to enable the development of analytical methods to characterize these nitrosaminerelated compounds.…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometry based fragmentation patterns of nitrosamine compounds

Asare

Hoskins

Blessing

et al. 2022

Rapid Comm Mass Spectrometry

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Rationale Nitrosamines are a class of mutagenic substances that can display high carcinogenic potential. New chemical entities may have the potential to form unique nitrosamines specific to the drug substance. It is therefore essential to understand the gas‐phase fragmentation behavior of nitrosamine compounds to enable the development of analytical methods to characterize novel nitrosamine compounds. Methods The gas‐phase fragmentation behavior of eight model nitrosamine compounds representing the common substructures seen in many small molecule pharmaceutical compounds was studied with positive electrospray ionization tandem mass spectrometry (ESI‐MS/MS). The fragmentation patterns of these compounds under various collision parameters available in commercially available mass spectrometers were studied. Results Protonated nitrosamine compounds produced diagnostic fragment ions upon MS/MS. Three primary structure‐dependent fragmentation pathways were observed. The first pathway involves the loss of 30 Da which corresponds to the loss of the NO radical from the protonated nitrosamine compound (Group 1). The second and third fragmentation pathways, which have not been reported for nitrosamine compounds, proceed via the loss of H2O from the protonated nitrosamine compound (Group 2), and elimination and a loss of 46 Da (loss of NH2NO) from the nitrosamine compound (Group 3). Conclusions Results presented in this work provide an overview of the gas‐phase fragmentation patterns of nitrosamine compounds and may be useful in identifying novel nitrosamine compounds in complex matrices.

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Simultaneous determination of tobacco minor alkaloids and tobacco‐specific nitrosamines in mainstream smoke by dispersive solid‐phase extraction coupled with ultra‐performance liquid chromatography/tandem orbitrap mass spectrometry

Abstract: The proposed method was suitable for analysis of tobacco minor alkaloids and tobacco-specific nitrosamines in cigarette mainstream smoke.

Cited by 13 publications

References 33 publications

LC/MS analysis of three-dimensional model cells exposed to cigarette smoke or aerosol from a novel tobacco vapor product

LC/MS analysis of three-dimensional model cells exposed to cigarette smoke or aerosol from a novel tobacco vapor product

Non-nicotine constituents in cigarette smoke extract enhance nicotine addiction through monoamine oxidase A inhibition

Mass spectrometry based fragmentation patterns of nitrosamine compounds

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