HPLC-FL. polycyclic aromatic hydrocarbon; PAH PAH PAH HPLC PAH HPLC US EPA DNA 4 US EPA. 2 1 US EPA 610 PAH Mix PAH PAH

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BUNSEKI KAGAKU Vol. 63, No. 1, pp. 23-292014 2014 The Japan Society for Analytical Chemistry 23 HPLC 1 1 1 Thanyarat CHUESAARD 2 1 1 1 polycyclic aromatic hydrocarbon; PAH 1 PAH / IARC PAH 2 10 46 PAH [a]bap 1 BaP DNA 3 IARC 1 4 US EPA PAH 16 26 PAH IARC PAH 5 PAH 4700 6 10 PAH 53 PAH 4 PAH PAH 7 SS PAH MS 10 PAH 8 PAH GC-MS 912 HPLC-FL 13 HPLC HPLC- E-mail : toriba@p.kanazawa-u.ac.jp 1 : 920-1192 2 : 920-1192 MS/MS 14 GC-MS HPLC-FL BaP GC-MS PAH S/N 3 10 pgbap 6 pg 15 MS HPLC PAH GC-MS HPLC BaP PAH US EPA 16 PAH 15 PAH HPLC-FL PAH 2 21 US EPA 610 PAH Mix EPA 16 15 PAH NapAce FlePheAnt FluPyr[a] BaAChr[b] BbF[k]BkFBaP [a,h]dbaha[ghi]bghip [1,2,3-cd]IDP IS 7 PAH -d 8 Nap-d 8 -d 10 Ace-d 10 -d 10 Phe-d 10 -d 10 Ant-d 10 -d 10 Pyr-d 10 [a]-d 12 BaA-d 12 [a]-d 12 BaP-d 12 HPLC Milli-Q

24 B U N S E K I K A G A K U Vol. 63 2014 22 3R4F 3R4F : JT ISO 4387 3308 1617 2 35 ml 1 1 1 810 5 1 DCM15 ml 2 mg 0.1 mg PAH 7 IS DCM/5/95, v/v 5 DCM DCM 10 ml 5 DCM Sep-Pak Silica 690 mg, Waters Sep-Pak Alumina-N1710 mg 5 DCM5 ml 10 DCM15 ml 35 DCM15 ml 5 10 DCM Fraction 135 DCM Fraction 2 DMSO 20 μl DMSO Fraction 1 480 μl Fraction 2 80 μl 20 μl HPLC 23HPLC HPLC NexeraLC-30AD SIL-30ACDGU-20A CTO-20ACCBM-20A RF-20A XSLabSolutions HPLCInertsil ODS-P3.0 mm i.d.250 mm, 5 μm, GL Sciences 3.0 mm i.d.10 mm 20 A: B: 010 B: 55 1017 B: 7090 linear 1735 B: 100 3545 B: 55 0.8 ml min 1 PAH 18 PAH 2 Pyr PAH 1 Pyr 2 3 31 PAH C 18 91012 1314 2 1920 Sep-Pak Silica Alumina-N PAH PAH 10 DCM PAH Fig. 1 21 PAH 2, 3 PAH4 PyrBaAChr 10 DCM BbFBkF 5, 6 PAH 35 DCM Fig. 1 5 DCM 10 DCM Fraction 1 35 DCM Fraction 2 Fraction 1 Fraction 2 DCM Nap 18 DCM- DCM DCM 5 PAH PAH

CHUESAARD : HPLC 25 Fig. 1 Elution profiles for PAHs with (A) silica and (B) Alumina-N SPE cartridges BaA Chr Fraction 2 PAH IS Fraction 1 Fraction 2 80 32 15 PAH Fig. 2A 15 PAH 7 IS 35 PAH IS ODS PAH PAH PAH IS 1822 Pyr Flu 2 S/N 3 Ant 0.24 pg IDP 2.2 pg 10 18 PAH GC-MS 915 Fig. 2B Nap Pyr 24 PAH Fraction 1 46 PAH Fraction 2 PAH Phe-d 10 IS-3 IS 33 6 IS Nap-d 8 Nap Ace-d 10 Ace, Fle Ant-d 10 Phe, AntPyr-d 10 Flu, PyrBaA-d 12 BaA, Chr BaP-d 12 BbF, BkF, BaP, DBahA, BghiP, IDP PAH 0.510 pg 2002000 pg

26 B U N S E K I K A G A K U Vol. 63 2014 Fig. 2 Chromatograms of (A) a standard solution of 15 PAHs and 7 internal standards prepared from EPA 610 polynuclear aromatic hydrocarbons mix (Sigma-Aldrich) and (B) representative chromatograms of a cigarette smoke sample. Chromatograms (A-1) and (A-2) were obtained from wavelength settings of the channel (CH) 1 and CH 2 for the standard solution. Chromatograms (B-1 and -2) and (B-3) were from CH 1 and 2 for the fraction 1 and CH 1 for fraction 2 of a real sample, respectively. Each peak of PAHs corresponds to: 1, Nap; 2, Ace; 3, Fle; 4, Phe; 5, Ant; 6, Flu; 7, Pyr; 8, BaA; 9, Chr; 10, BbF; 11, BkF; 12, BaP; 13, DBahA; 14, BghiP; 15, IDP. IS-1, IS-2, IS-3, IS-4, IS-5, IS-6 and IS-7 indicate Nap-d 8, Ace-d 10, Phe-d 10, Ant-d 10, Pyr-d 10, BaA-d 12 and BaP-d 12, respectively. The detection wavelength programs were as follows: (CH 1) 0 15.3 min, excitation (Ex) 280 nm, emission (Em) 340 nm; 15.3 16.85 min, Ex 250 nm, Em 400 nm; 16.85 19 min, Ex 286, Em 433 nm; 19 30.9 min, Ex 264, Em 407 nm; 30.9 35 min, Ex 294 nm, Em 482 nm; (CH 2) 0 35 min, Ex 331 nm, Em 392 nm. The other HPLC conditions were the same as those described in the Experimental section. r 2 0.999 PAH S/N 10 Ant 0.073 pg IDP 7.5 pg PAH Table 1 PAH n 5 0.6810 Accuracyn 5 85111 15 PAH Phe 2 34 PAH 3R4F TPM PAH Table 2 3 PAH 0.2305 ng cigarette 1 26.4 6160 ng cigarette 1 PAH 2, 3 PAH 46 PAH NapFle Phe 1012 Fle Fle 23 3 PAH PAH

CHUESAARD : HPLC 27 Table 1 Precision and accuracy in the determination of PAHs in cigarette smoke samples (n 5) Nap Ace Added amounts/ng mg 1 0 24.6 0 24.6 FoundSD/ng mg 1 15.00.34 37.60.62 0.890.03 25.10.21 RSD/ 2.2 1.7 3.3 0.83 Accuracy/ 92 99 Fle Phe Added amounts/ng mg 1 0 29.4 0 28.7 FoundSD/ng mg 1 17.30.32 49.61.16 48.60.29 78.81.43 RSD/ 1.8 2.3 0.59 1.8 Accuracy/ 110 105 Ant Flu Added amounts/ng mg 1 0 2.5 0 4.9 FoundSD/ng mg 1 2.30.03 5.00.11 2.60.10 7.40.45 RSD/ 1.2 2.2 3.8 6.0 Accuracy/ 110 98 Pyr BaA Added amounts/ng mg 1 0 2.5 0 2.5 FoundSD/ng mg 1 2.00.05 4.70.11 1.10.06 3.30.06 RSD/ 2.6 2.3 5.6 1.7 Accuracy/ 111 89 Chr BbF Added amounts/ng mg 1 0 2.5 0 4.9 FoundSD/ng mg 1 0.70.03 2.80.05 0.20.02 4.30.07 RSD/ 3.9 1.7 10 1.8 Accuracy/ 86 85 BkF BaP Added amounts/ng mg 1 0 2.5 0 2.5 FoundSD/ng mg 1 0.20.01 2.50.04 0.50.02 2.90.02 RSD/ 5.4 1.5 4.4 0.68 Accuracy/ 95 98 DBahA BghiP Added amounts/ng mg 1 0 4.9 0 4.9 FoundSD/ng mg 1 n.d. a) 5.00.05 LOQ b) 4.60.08 RSD/ 1.0 1.8 Accuracy/ 102 94 IDP Added amounts/ng mg 1 0 2.5 FoundSD/ng mg 1 0.20.01 2.60.05 RSD/ 4.7 2.0 Accuracy/ 98 a) n.d., not detected.; b) below the limit of quantification. PAH 4924 DBahA DBahA 3R4F PAH 9 r 0.859, p 0.01 3 PAH r 0.9280.974, p 0.01 PAH TPM SS/ MS 23 PAH SS/MS 19 IARC 2 1 BaP 14 2B BaAChrBbFBkFIDP 1481 Table 24 PAH 10 24 IARC 1 4

28 B U N S E K I K A G A K U Vol. 63 2014 Table 2 Total particulate matter (TPM) (mg cigarette 1 ) and PAH levels (ng cigarette 1, meansd) in mainstream (MS) and sidestream (SS) smoke from 3 cigarette brands 3R4F Marlboro MILD SEVEN Analyte Mainstream (MS) Sidestream (SS) Ratio (SS/MS) Mainstream (MS) Sidestream (SS) Ratio (SS/MS) Mainstream (MS) Sidestream (SS) Ratio (SS/MS) TPM 11.00.2 29.11.1 3 11.50.1 23.30.9 2 14.40.2 25.60.9 2 Nap 1565 2460246 16 17413 220084.6 13 1177.5 2170256 19 Ace 14.05.8 1306 9 9.80.3 99.08.9 10 7.31.6 10013 14 Fle 2137 6160218 29 30527 5240270 17 2169.8 570046 26 Phe 95.12.7 4350141 46 79.63.0 261073.0 33 98.20.7 335047 34 Ant 3.40.3 2029 60 5.40.5 19028.9 35 3.70.2 1499 41 Flu 21.40.7 67314 31 32.10.4 68882.0 21 25.21.4 63826 25 Pyr 18.00.3 49626 28 27.10.4 44517.6 16 23.10.7 47723 21 BaA 10.50.8 54222 52 13.21.3 41671.8 31 8.90.5 41130 46 Chr 8.10.4 45266 56 11.00.5 42552.5 38 8.90.1 35919 40 BbF 1.30.3 1046 81 3.10.5 81.511.0 26 2.80.1 89.57.8 32 BkF 1.00.2 45.22.7 45 2.30.2 33.04.8 14 2.20.0 42.22.4 19 BaP 5.30.1 1117 21 6.90.3 96.16.2 14 5.70.2 1026 18 DBahA n.d. a) n.d. n.d. n.d. n.d. n.d. BghiP 0.20.1 26.42.5 152 0.80.1 30.52.0 38 0.70.2 32.21.6 46 IDP 1.30.3 35.60.7 28 3.30.2 51.85.2 15 2.40.5 44.46.9 19 total 54816 15800406 29 67341 12600217 19 52217 13700787 26 a) n.d., not detected. PAH PAH 14 4 HPLC-FL 15 PAH ODS PAH PAH GC-MS PAH 5RF-1302B23406004 1) : (Bunseki), 2008, 278. 2) IARC : Monographs on the Evaluation of Carcinogenic Risks to Humans, http://monographs.iarc.fr/ ENG/Classification/index.phpaccessed 16 July 2013. 3) K. B. Kim, B. M. Lee : Cancer Lett., 113, 205 (1997). 4) IARC : Tobacco Smoke and Involuntary Smoking, Monographs on the Evaluation of Carcinogenic Risks to Humans 83, p. 1 (2004), (Lyon, France). 5) USEPA : Priority Pollutants 40 CFR, Protection of Environment Appendix A to Part 423, (2010), (Washington, DC, USA). 6) R. F. Casper, M. Quesne, I. M. Rogers, T. Shirota, A. Jolivet, E. Milgrom, J. F. Savouret : Mol. Pharmacol., 56, 784 (1999). 7) M. Kalaitzoglou, C. Samara : Food Chem. Toxicol., 44, 1432 (2006). 8) H. Lee, D. P. H. Hsieh, L. Li : Chemosphere, 82, 477 (2011). 9) J. E. Tarrant, K. Mills, C. Williard : J. Chromatogr. A, 1216, 2227 (2009). 10) G. Gmeiner, G. Stehlik, H. Tausch : J. Chromatogr. A, 767, 163 (1997). 11) J. B. Forehand, G. L. Dooly, S. C. Moldoveanu : J. Chromatogr. A, 898, 111 (2000). 12) Y. S. Ding, J. S. Trommel, X. J. Yan, D. Ashley, C. H. Watson : Environ. Sci. Technol., 39, 471 (2005). 13) J. Dumont, F. Larocque-Lazure, C. Iorio : J. Chrmatogr. Sci., 31, 371 (1993). 14) Y. S. Ding, D. L. Ashley, C. H. Watson : J. Agric. Food Chem., 55, 5966 (2007). 15) C. Stader, F. T. Beer, C. Achten : Anal. Bioanal. Chem., 405, 7041 (2013). 16) International Standard : ISO Standard 4387, Third ed. (2000).

CHUESAARD : HPLC 29 17) International Standard : ISO Standard 3308, Forth ed. (2000). 18) A. Toriba, Y. Kuramae, T. Chetiyanukornkul, R. Kizu, T. Makino, H. Nakazawa, K. Hayakawa : Biomed. Chromatogr., 17, 126 (2003). 19) G. Shen, S. Tao, S. Wei, Y. Zhang, R. Wang, B. Wang, W. Li, H. Shen, Y. Huang, Y. Chen, H. Chen, Y. Yang, W. Wang, X. Wang, W. Liu, S. L. M. Simonich : Environ. Sci. Technol., 46, 8123 (2012). 20) L. Liu, Y. Liu, J. Lin, N. Tang, K. Hayakawa, T. Maeda : J. Environ. Sci., 19, 1 (2007). 21) M. E. Machado, L. P. Bregles, E. W. de Menezes, E. B. Caramão, E. V. Benvenutti, C. A. Zini : J. Chromatogr. A, 1274, 165 (2013). 22) S. A. Wise, L. C. Sander, W. E. May : J. Chromatogr., 642, 329 (1993). 23) A. Toriba, T. Chetiyanukornkul, R. Kizu, K. Hayakawa : Analyst, 128, 605 (2003). 24) M. Lodovici, V. Akpan, C. Evangelisti, P. Dolara : J. Appl. Toxicol., 24, 277 (2004). Quantification of Polycyclic Aromatic Hydrocarbons (PAHs) in Cigarette Smoke Particulates by HPLC with Fluorescence Detection Akira TORIBA 1, Chiharu HONMA 1, Waka UOZAKI 1, Thanyarat CHUESAARD 2, Ning TANG 1 and Kazuichi HAYAKAWA 1 E-mail : toriba@p.kanazawa-u.ac.jp 1 Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa-shi, Ishikawa 920-1192 2 Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa-shi, Ishikawa 920-1192 (Received October 4, 2013; Accepted November 18, 2013) A high-performance liquid chromatographic (HPLC) method with fluorescence detection was developed for the quantification of polycyclic aromatic hydrocarbons (PAHs) in cigarette mainstream and sidestream smoke particulates. Fifteen kinds of PAHs classified as priority pollutants by the US EPA were quantified with six perdeuterated PAHs as internal standards. The smoke filter samples obtained from 3 brands of cigarettes using standardized smoking conditions were extracted with dichloromethane, and then treated with tandem solid phase extraction cartridges (Silica and Neutral Alumina). The limits of detection ranged from 0.24 to 2.2 pg, and were more sensitive than those by GC-MS. The analytes were quantified by using the internal standards, and the developed method achieved sufficient reproducibility and accuracy. The PAH levels in mainstream and sidestream smoke from 3 cigarette brands were in the range of 0.2 305 ng cigarette 1 and 26.4 6160 ng cigarette 1, respectively. The total PAH content in sidestream smoke was more than 10 times higher compared with that of mainstream smoke. This method should be useful as an optional analytical method to quantify PAHs in cigarette smoke particulates. Keywords: polycyclic aromatic hydrocarbon; cigarette smoke; HPLC; fluorescence detection; solid phase extraction.