A sensitive and accurate method for the quantification of 1 -Demethyl-1 -nitrosonicotine (NNN) and 4-(methylnitrosamino)-1-(3-Pyridyl)-1-butanone (NNK) in indoor air was developed and validated. To this aim, a novel approach for the collection of two tobacco-specific nitrosamines, using silica sorbent cartridges followed by simplified sample preparation and isotope dilution liquid chromatography/electrospray ionization tandem mass spectrometry, was applied.
Trang 1María Gómez Luesoa, Maya I Mitovaa,∗, Nicolas Mottiera,b, Mathieu Schallera,
Michel Rotacha, Catherine G Goujon-Ginglingera
a PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland
b Service de la Consommation et des Affaires Vétérinaires, Chemin des Boveresses 155, 1066 Epalinges, Switzerland
a r t i c l e i n f o
Article history:
Received 13 July 2018
Received in revised form
28 September 2018
Accepted 17 October 2018
Available online 23 October 2018
Keywords:
Tobacco-specific nitrosamines
Validation
Accuracy profile
Environmental aerosol
Tobacco heating system
e-Cigarette
a b s t r a c t
Asensitiveandaccuratemethodforthequantificationof1-Demethyl-1-nitrosonicotine(NNN)and 4-(methylnitrosamino)-1-(3-Pyridyl)-1-butanone(NNK) inindoor airwasdeveloped and validated
Tothisaim, anovel approach forthecollection oftwo tobacco-specificnitrosamines, usingsilica sorbentcartridgesfollowedbysimplifiedsamplepreparationandisotopedilutionliquid chromatogra-phy/electrosprayionizationtandemmassspectrometry,wasapplied.Thisprocedureledtoasubstantial improvementintermsofsensitivityandsamplethroughputascomparedwithmethodsusing conven-tionaltrapping.Forthevalidation,amatrix-basedapproachusinganaccuracyprofileprocedurewas selected.Theevaluatedmatriceswerebackgroundairsamples,environmentalaerosolsofa heat-not-burntobaccoproduct(TobaccoHeatingSystem[THS]2.2,commercializedunderthebrandIQOS®),a rechargeableelectroniccigarette(Solaris®),andtheenvironmentaltobaccosmoke(ETS)ofa conven-tionalcigarette(MarlboroGold®).Themethodshowedexcellentrecoveries,sensitivity,andprecision.The limitsofdetectionofthemethodforNNNandNNKwere0.0108ng/m3and0.0136ng/m3,respectively Thecalibrationrangeoftheinstrumentspanned0.2–60ng/mL.Thecalculatedlowerworkingrangelimit (LWRL)ofthemethodforNNNwas0.126ng/m3,andtheLWRLforNNKwas0.195ng/m3.Themethodwas appliedtoevaluatesurrogateenvironmentalaerosolsgeneratedusingsmokingmachines.Thismodelis reliablebutgivesalargeoverestimationofthepossibleimpactofTHS2.2ande-cigarettesonindoorair, becausetheretentionofNNNandNNKinthebodyoftheconsumersisnottakenintoaccount.Asa con-sequence,thevaluesreporteddonotreflectareal-lifesetting.Thecontentsofthetwotargetcompounds
inthesurrogateenvironmentalaerosolswere0.0830±0.0153ng/m3ofNNNand0.0653±0.0138ng/m3
ofNNKforTHS2.2,0.0561±0.0296ng/m3ofNNNfore-cigarettes,and0.816±0.109ng/m3ofNNNand 4.13±1.04ng/m3NNKforcigarettes.Thesevaluescorrespondto10%ofthemeasuredETSconcentration forNNNinenvironmentalaerosolsofTHS2.2and7%forthoseofe-cigarettes.ForNNK,thevalueforthe environmentalaerosolofTHS2.2was2%oftheETSvalue
©2018PMIR&D,PhilipMorrisProductsS.A.,QuaiJeanrenaud5,2000Neuchâtel,Switzerland PublishedbyElsevierB.V.ThisisanopenaccessarticleundertheCCBYlicense(http://
creativecommons.org/licenses/by/4.0/)
1 Introduction
4-(methylnitrosamino)-1-(3-Pyridyl)-∗ Corresponding author.
E-mail address: Maya.Mitova@pmi.com (M.I Mitova).
grow-https://doi.org/10.1016/j.chroma.2018.10.037
0021-9673/© 2018 PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland Published by Elsevier B.V This is an open access article under the
Trang 2[3,4] Thisprocess occursmostly during theprocessing, curing,
1–29ng/m3)[10–13]
anal-yses[13,24,34,36].Asaconsequence,methodswithLLOQabove
[13,36]
2 Material and methods
Trang 3preparation
samples
3 Results and discussion
Trang 4The instrument chosen for the analysis was an LC-20A
Fig 1. Typical chromatogram for NNN and NNK The blue trace represents the NNN transition used as quantifier (178/148) The red trace represents the NNN transition used as qualifier (178/120) The green trace represents the NNN-D 4 tran-sition (182/152) The grey trace represents the NNK transition used as quantifier (208.1/121.7) The light blue trace represents the NNK transition used as qualifier (208.1/79) The pink trace represents the NNK-D 4 transition (211.8/126).
Trang 5recoveries
Trang 6Table 1
Data used to build the accuracy profiles for NNN.
Matrix 1 Spiking level Spikingconcentration
[g/mL]
Trueness values per series
CV r CV R 80% Tolerance Interval
1 2 3 4 Average Lower limit Upper limit
BKG
Level 1 0.229 142 107 144 131 131 7 18 100 161 Level 2 0.514 107 101 126 113 112 4 11 93 131 Level 3 0.883 117 95 114 107 108 3 10 90 126 Level 4 1.66 109 109 106 105 107 2 2 104 111 Level 5 3.41 103 104 103 100 103 2 2 99 106 Level 6 4.97 103 101 103 100 102 2 2 99 105
EA of THS2.2
Level 1 0.229 131 30 135 90 96 14 50 7 186 Level 2 0.514 101 64 114 112 98 7 24 56 139 Level 3 0.883 113 70 113 100 99 4 20 62 136 Level 4 1.66 103 93 95 93 96 2 5 87 105 Level 5 3.41 103 94 96 95 97 2 5 90 105 Level 6 4.97 102 94 96 96 97 2 4 91 103
ETS
Level 1 0.989 89 119 103 130 110 9 20 78 143 Level 2 1.977 91 101 106 93 97 4 8 84 110 Level 3 4.945 98 95 99 90 95 2 4 88 103 Level 4 7.97 104 97 103 94 99 1 5 91 108 Level 5 15.93 106 99 98 99 101 2 4 94 107 Level 6 30.10 100 99 98 97 98 2 2 95 102
EA fo e-cig
Level 1 0.229 94 123 93 72 95 16 25 56 135 Level 2 0.514 96 118 103 96 103 10 14 83 124 Level 3 0.883 96 110 101 100 102 6 8 90 113 Level 4 1.66 106 109 105 105 106 3 3 102 111 Level 5 3.41 103 103 101 104 103 3 3 99 107 Level 6 4.97 104 105 102 105 104 2 2 101 107
1 BKG: Background, EA: Environmental Aerosol, ETS: Environmental Tobacco Smoke.
[44,45]
[44–46].Thelowerworkingrangelimit(LWRL)andupperworking
Table1containsthedatausedtobuildtheaccuracyprofiles
Table2containsthedatausedtobuildtheaccuracyprofiles
Trang 7Table 2
Data used to build the accuracy profiles for NNK.
Matrix 1 Spiking level Spikingconcentration
[g/mL]
Trueness values per series
CV r CV R 80% Tolerance Interval
1 BKG: Background, EA: Environmental Aerosol, ETS: Environmental Tobacco Smoke.
Table 3
Lower Working Range Limits (LWRL) and Upper Working Range Limits (UWRL) for
NNN and NNK.
Matrix 1 Target
compound
LWRL 2 UWRL 2
ng/mL ng/m 3 ng/mL ng/m 3
BKG NNN 0.919 0.255 60.2 16.7
NNK 1.30 0.362 60.6 16.8
EA of THS2.2 NNN 1.16 0.322 60.2 16.7
NNK 0.702 0.195 60.6 16.8
ETS NNN 1.37 0.379 60.2 16.7
NNK 5.24 1.46 60.6 16.8
EA of e-cig NNN 0.453 0.126 60.2 16.7
NNK 0.994 0.276 60.6 16.8
Min NNN 0.453 0.126 60.2 16.7
Max NNK 0.702 0.195 60.6 16.8
1 BKG: Background, EA: Environmental Aerosol, ETS: Environmental Tobacco
Smoke.
2 Conversion from ng/mL to ng/m 3 using 1.5 L/min sampling flow-rate and four
hours of collection (0.36 m 3 ), and final solution volume of 0.1 mL.
Table3presentstheLWRLandUWRLforthetwotarget
e-cigarettes
Table4presentstheaverageNNNandNNKmatrixendogenous
[12,13,22,23,34]aswellasinreal-lifeconditions[12].In
Trang 8Table 4
Average content of NNN and NNK in Background, environmental aerosol of THS 2.2 and e-cigarette, and environmental tobacco smoke (smoking machine model).
Matrix 1
Average endogenous content
in homogenized matrix
Average endogenous content
in non- homogenized matrix
Average endogenous content per matrix type (all values)
ng/m 3 ng/m 3 ng/m 3 ng/m 3 ng/m 3 ng/m 3
BKG Average <0.0108 3 <0.0136 3 <0.0108 3 <0.0136 3 <0.0108 3 <0.0136 3
EA of THS2.2 Average 0.0849 2 0.0683 2 0.0792 2 0.0593 2 0.0830 2 0.0653 2
STDEV 0.0155 0.0136 0.0149 0.0125 0.0153 0.0138
EA of e-cig Average 0.0557 2 <0.0136 3 0.0570 2 <0.0136 3 0.0561 2 <0.0136 3
ETS Average 0.819 4.121 0.811 4.140 0.816 4.127
STDEV 0.108 0.941 0.114 1.253 0.109 1.042
1 BKG: Background, EA: Environmental Aerosol, ETS: Environmental Tobacco Smoke.
2 Average values are between the LLOQ and the LWRL of the method, accuracy outside ±25% threshold.
3 Average values under LOD (the displayed value corresponds to the LOD).
Fig 2.Accuracy profiles obtained for NNN in a) the background air sample, b) EA of
THS 2.2, c) EA of e-cig, and d) ETS of Marlboro Gold samples Legend: average
recov-ered concentration per spiking level (black circle), trueness expressed as recoveries
(orange spots line), upper and lower -expectation tolerance intervals (blue
contin-uous lines), upper and lower acceptance limits set at 25% (red dashed lines), average
NNK nominal concentration (green square), LWRL (green vertical dashed line).
Fig 3. Accuracy profiles obtained for NNK in a) the background air sample, b) EA of THS 2.2, c) EA of e-cig, and d) ETS of Marlboro Gold samples Legend: average recov-ered concentration per spiking level (black circle), trueness expressed as recoveries (orange spots line), upper and lower -expectation tolerance intervals (blue contin-uous lines), upper and lower acceptance limits set at 25% (red dashed lines), average NNK nominal concentration (green square), LWRL (green vertical dashed line).
Trang 9theexperimentsofAdlkoferetal.[22] runina45m3 office for
(Table4).Theseconcentrationscorrespondedtovaluesbetween
4 Conclusions
cigarettes
Conflict of interest
Funding
Appendix A Supplementary data
037
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