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KOREAN J. FOOD SCI. TECHNOL. Vol. 42, No. 3, pp. 257~262 (2010) š (SPE: Solid Phase Extraction) w ü Patulin rá ÁxÁŸ * w tœw The Korean Society of Food Science and Technology Rapid and Simple Analytical Method for Removing Patulin from Apple Juice Using Solid Phase Extraction JongGab Yim, HaeWon Jang, and KwangGeun Lee* Department of Food Science and Technology, Dongguk UniversitySeoul Abstract Patulin, a secondary metabolite of mold, is commonly found in rotten apples. Many countries regulate patulin at levels ranging from 30 to 50 µg/l. Most analytical methods for removing patulin from apple juice include liquidliquid extraction (LLE), which is time and labor intensive. To replace the LLE method, a solidphase extraction (SPE) method has been developed for apple juice and unfiltered apple juice. A portion of the test sample was applied to a macroporous copolymer cartridge and washed with 5 ml of 1% sodium bicarbonate, followed by 5 ml of 1% acetic acid. Patulin was eluted with 5 ml of 2% acetonitrile in anhydrous ethyl ether. The mobile phase was tetrahydrofuran in water (0.8:99.2) and was detected with a UV detector at 276 nm. Recoveries ranged from 95 to 101% in test samples, and the minimum detectable level was 30 ppb. Because this SPE method is fast, easy, reliable, and inexpensive, it could be applicable for companies or analytical agencies to analyze patulin concentrations in apple juice. Key words: Solid Phase Extraction, Apple juice, HPLC, Patulin x, ƒœt, w ƒ ³ w ƒ w ƒ š. q š wù»ƒ w q š, t. y» mw w(1,2). x¾ 300400 q ƒ, tù w ww w q 1020 ƒ (3). q w p ƒ š aflatoxin, ochratoxin A, sterigmatocystin, patulin, penicillic acid, citrinin, zearalenone, trichothecenes(t2 toxin) (4). patulin(2hydroxy3,7dioxabicyclo[4.3.0]nona 5,9dien8one) q³ Penicillium expansum sww, P. griseofulvum, P. patulum Aspergillus clavatus, A. terreus, A, giganteus, Bassochlamys fulva, B. nivea 30 60 q w (5,6) P. expansum patulin *Corresponding author: KwangGeun Lee, Department of Food Science and Technology, Dongguk UniversitySeoul, Seoul 100715, Korea Tel: 82222603370 Fax: 82222853370 Email: kwglee@dongguk.edu Received October 22, 2009; revised January 12, 2010; accepted January 22, 2010 w ƒ w q(7). Patulin w q (8) s,,. Patulin aflatoxin q w ûš ù, y» w p ƒw ùkü. 1961 w x (Dickens and Jones) patulin w z(9), IARC( ) w 3 (8). Mice w LD 50 0.3 mg/20 g(vw), 0.5 mg/20 g(), 0.7 mg/20 g( )š, rat n 4 ü ew. FAO WHO w tƒƒz(the Joint of FAO/ WHO Expert Community on Food Additives: JECFA) patulin x(tdi: Tolerable Daily Intake) 0.4 µg/kg body weight w(10), ù w 50 µg/kg body weight/day x w(tt š 2004 18y). t sƒ w yš, z patulin y w. Patulin p yრš w ƒ y. Patulin w LLE(liquidliquid extraction) yw wš w w w ƒ w w w. w» ƒ vw» w y ƒ, xƒ» 257

258 w twz 42 «3y (2010) ƒ j ƒ j š (11). SPE(solidphase extraction) liquid xk solid phase(š) k z w k kj. cartridge w j x wš w w (12,13). w, SPE cartridge column k. x tœ x LLE w x š w x š. ƒ š AOAC ethyl acetate patulin wš sodium bicarbonate zw LLE (14). LLE w z kwš w. w m ü 3ƒ tœ LLE, ƒ SPE cartridge(strata/merck) w ww. x w t 3 t w 100% ü t x p w w, þ(5 o C) w. t x w patulin t Sigma(St. Louis, MO, USA) wš, ethyl acetate(hplc grade), water(hplc grade), acetic acid, acetonitrile, tetrahydrofuran(thf, HPLC grade) Burdick & Jackson t(muskegon, MI, USA) w. Sodium bicarbonate k Wako(Wako, Tokyo, Japan) t w. t Patulin ethyl acetate ww z 200 µg/ml ƒ w t w. t y w z þ w w. t t 0.1, 0.2, 0.5, 1.0 µg/ml ƒ ƒ m j z w w þ w w. x Mobile phase tetrahydrofuran(thf, HPLC glade) 8 ml 1L vj š 3 w. 3 acetic acid ph 4.0 w w, 1.5%(w/v) sodium bicarbonate sodium bicarbonate 1.5 g 3 100 ml w. LLE(liquidliquid extraction) LLE 5g x(i) y w ethyl acetate 10 ml š 1 z ew Pasteur pipette d x(ii). x(i) ethyl acetate 10 ml š 1 z ew d x(ii) ww. ethyl acetate 1.5% sodium bicarbonate 2mL š ew z d Pasteur pipette x(iii) Table 1. Analytical conditions for patulin using HPLC Items Conditions Instrument HPLC (Shiseido Nanospace) Column C 18 (4.6 250 mm, 5 µm) Flow rate 0.7 ml/min Injection volume 20 µl Mobile phase THF:Water (0.8:99.2) Run time 25 min Detector UV Detector (276 nm) ¼. x(ii) ethyl acetate 5 ml š ew z d x(iii) ww. ethyl acetate sodium sulfate 1 g š 30 z d x(iv) w z ethyl acetate acetic acid 0.5 ml ww x w. SPE(solidphase extraction) StrataX SPE StrataX cartridge column 3 7 ml ü z methanol 7 ml y(conditioning) g. y column 5mL loading k z 1% sodium bicarbonate 5 ml 1% acetic acid 5 ml w w óù column 1 ew z ethyl acetate/ethyl ether 5 ml w w.» w w z 1% acetic acid 0.5 ml š yw(vortexing)w z syringe filter w amber vial w w. SPE(solidphase extraction) Merck Merck Extrelut NT20 cartridge y column loading w z 20 ƒ ew ethyl acetate /ethyl ether w w» z 1% acetic acid 0.5 ml š yww z w. HPLC Shiseido HPLC Nanospace SI2 Shiseido Nanospace 3002 UV Detector w w, column Shiseido C 18 (4.6 250 mm, 5 µm) column kw w. Mobile phase (THF 8 ml/water 1 L) 0.7 ml/min 276 nm Ÿ dwš(table 1), patulin peak patulin tš w patulin w w. š z x LLE w, yw wš w w w q (mycotoxin), Polycyclic Aromatic Hydrocarbons(PAHs) ƒ x š. x w mw w w y z HPLC. LLE w patulin ƒw patulin t 200 ng/ml 500 ng/ml

Table 2. Recovery rates of patulin using LLE and SPE ü rá Patulin 259 Added (ng/ml) SPE LLE StrataX ExtrelutNT20 Recovery (%) SD 1) (%) RSD 2) (%) Recovery (%) SD (%) RSD (%) Recovery (%) SD (%) RSD (%) 200 106 11.4 10.8 101 9.7 9.6 101 12.1 12.0 500 92 2.9 3.2 96 1.2 1.2 95 4.7 5.0 1) Standard deviation 2) Calculated as (standard deviation/mean) 100, expressed as the coefficient of variance (%CV) Fig. 1. HPLC chromatogram of patulin in apple juice using LLE method. (A) standard, (B) apple juice I, (C) apple juice II and (D) apple juice III. w 92106% z š(table 2), x w ü (w 100%) w patulin 1315 w peakƒ ƒ yw (Fig. 1). Patulin ƒ w» w wš š(17). (18) LLE mw x» 50 µg/kg šw,, patulin ƒ(spiking)w z dw, ƒƒ 8592%, 9799%, 100104% z. w (LOD: limit of detection) y ƒ(signal/noise, S/N)ƒ 3 w wš 30 ng/ml. SPE LLE wù w, rw wš yw w w t y š. x 200 SPE cartridgeƒ Phenomenex StrataX Merck Extrelut NT 20 w x ww. StrataX SPE w y ƒ w 12 w» w vacuum pumpù syringe cartridge w ƒw w(19). x vacuum pump w ww w ƒw. ü A, B, C w patulin ƒƒ 1.53.2 ng/ml, z 96101% (Table 3, Fig. 2). Li (20) Agilent Technologies AccuBoII ODSCartridge w SPE mw patulin w 96.4 114.1% z ùküš, SPE patulin kwš yw. Cho (17), GonzlezOsnaya (21) š w ü patulin w 50 ng/ml w šš. SPE 1 t ƒ, cartridge y j» w (22). ExtrelutNT20 y cartridge t w vƒ š, w vacuum pumpù syringe w j w. Patulin t peak

260 w twz 42 «3y (2010) Table 3. Concentrations of patulin in apple juice using various extraction methods Apple juice Concentration (ppb) LLE SD 1) (%) RSD 2) (%) Concentration (ppb) StrataX SD (%) RSD (%) SPE Concentration (ppb) ExtrelutNT20 SD (%) RSD (%) A B C 1.6 3.2 2.2 6.1 3.2 5.8 38.1 10.0 26.4 1) 3) 1.5 6.5 43.3 1) Standard deviation 2) Calculated as (standard deviation/mean) 100, expressed as the coefficient of variance (%CV) 3) Not detected Fig. 2. HPLC chromatogram of patulin in apple juice using SPE (stratax) method. (A) standard, (B) apple juice I, (C) apple juice II and (D) apple juice III., ƒwù, ü A, B, C patulin (Fig. 3). j LLEù StrataX w û, ü w ƒ. x z Patulin t w š ü (R 2 ) 0.9998, w 30.0 ng/ml d. HPLC mw mobile phase tetrahydrofuran(thf) ƒ w xw 3 THF 8 ml w g 1 L w ƒ chromatogram pattern.»» HPLC column k w ƒ patulin 3.0 250 mm 4.6 250 mm C 18 column w ƒ. 3.0 250 mm C 18 column w patulin 67 j 4.6 250 mm C 18 column 7 (RT) yw. w, patulin w y HMF(Hydroxy methyl furfural) peakƒ w. 4.6 250 mm C 18 column w w v patulin 1315 ùk û, HMF 1 yw (Fig. 4). Li (20), Gaspar (23) š w patulin wj» w 4.6 250 mm C 18 column w. LLE SPE w z LLE 92106%, SPE strataxƒ 96101% ExtrelutNT20 95101% z»(acceptance criteria) j ùkû(table 1). š SPE w t r strataxƒ 1.29.7%, ExtrelutNT20 4.712.1%

ü rá Patulin 261 Fig 3. HPLC chromatogram of patulin in apple juice using SPE (ExtrelutNT20) method. (A) standard, (B) apple juice I, (C) apple juice II and (D) apple juice III.. strataxƒ 1.29.6%, ExtrelutNT20 5.0 12.0% w. Fig. 4. HPLC chromatogram of patulin using various C18 columns. (A) 3.0 250 mm C 18 column, (B) 4.6 250 mm C 18 column. Patulin q. sw patulin w x LLE w. w» w SPE mw patulin ww. œ w š ep w z 1% sodium bicarbonate 5mL 1% acetic acid 5 ml w w ƒ óù ep 1 ew z ethyl acetate/ethyl ether 5 ml w w.» w w z 1% acetic acid 0.5 ml š yw z syringe filter w amber vial w w. HPLC THF 8 ml 1L v j š w. HPLC 0.7 ml/min 276 nm Ÿ dwš, v 20 µg/l w. LOD 30 ng/ml. x SPE» tœx(lle) 1/ 3 š, ƒ ƒw x w œ w. p, stratax mw SPE z w w ww.» w wš w yw w z w»

262 w twz 42 «3y (2010) z. w w w. x 1. Train A, Rosell MG, Guardino X. Use of highperformance liquid chromatography to assess airborne mycotoxins: Aflatoxin and ochratoxin A. J. Chromatogr. A 1047: 235240 (2004) 2. Dorner JW, Cole RJ, Connick WJ, Daigle DJ, McGuire MR, Shasha BS. Evaluation of biological control formulations to reduce aflatoxin contamination in peanuts. Biol. Control 26: 318 324 (2003) 3. Rief K, Metzger W. Determination of aflatoxins in medicinal herbs and plant extracts. J. Chromatogr. A 692: 131136 (1995) 4. Park KY. Factors affecting aflatoxin production. J. Korean Soc. Food Nutr. 13: 117126 (1984) 5.Papp E, HOtta K, Zaray G, Mincsovics E. Liquid chromatographic determination of aflatoxins. J. Microchem. 73: 3946 (2002) 6. Harrison MA. Presence and stability of patulin in apple products: A review. J. Food Safety 9: 147153 (1989) 7. Steiman R, SeigleMurandi F, Sage L, Krivobok S. Production of patulin by micromycetes. Mycopathologia 105: 129133 (1989) 8. IARC. Patulin, IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, International Agency for Research on Cancer, Lyon, France. 40: 8398 (1986) 9. Ukai T, Yamamoto Y, Yamamoto T. Studies on the poisonous substance from a strain of Penicillium, II. Culture method of Hori Yamamoto strain and chemical structure of its poisonous substance. J. Pharmacol. Sci. 74: 450454 (1954) 10. Rief K, Metzger W. Determination of aflatoxins in medicinal herbs and plant extracts. J. Chromatogr. A 692: 131136 (1995) 11. Trucksess MW, Tang Y. Solidphase extraction method for patulin in apple juice and unfiltered apple juice. J. AOAC Int. 82: 1109 1113 (1999) 12. Gil BD. Poisoning and preventive measures caused by organic solvent. Ind. Health 5: 3034 (1997) 13. Huand Z, Zhang S. Confirmation of amphetamine, methamphetamine, MDA, and MDMA in urine samples using disk solidphase extraction and gas chromatographymass spectrometry after immunoassay screening. J. Chromatogr. B 792: 241247 (2003) 14. AOAC, Official Methods of Analysis of AOAC International 16th ed. Method 995.10. Association of Official Analytical Chemists International, Gaithersburg, MD, USA (1997) 15. Lee MR, Yu SC, Lin CL, Hu SH. Solidphase extraction in amphetamine and methamphetamine analysis of urine. J. Anal. Toxicol. 21: 278282 (1997) 16. Fidente P, Seccia S, Vanni F, Morrica P. Analysis of nicotinoid insecticides residues in honey by solid matrix partition cleanup and liquid chromatographyelectrospray mass spectrometry. J. Chromatogr. A 1094: 175178 (2005) 17. Cho WI, Choi YB, Moon TW. Determination of patulin in commercial apple juice in Korea by high performance liquid chromatography. Korean J. Food Sci. Technol. 29: 412415 (1997) 18. Eom JH, Byun JA, Park YG, Seo EC, Lee EM, Kim MR, Sun NK, Kim CS, Jung WY, Jung RS, Na MA, Lee JH. Monitoring of patuliln levels in fruit juices and beverages. J. Fd Hyg. Safety 24: 5662 (2009) 19. Österdahl BG, Johnsson H, Nordlander I. Rapid extrelut column method for determination of levamisole in milk using highperformance liquid chromatography. J. Chromatogr. 337: 151155 (1985) 20. Li JK, Wu RN, Hu QH, Wang JH. Solidphase extraction and HPLC determination of patulin in apple juice concentrate. Food Control 18: 530534 (2007) 21. GonzálezOsnaya L, Soriano JM, Moltó JC, Mañes J. Exposure to patulin from consumption of applebased products. Food Addit. Contam. 24: 12681274 (2007) 22. Thomas AE, Midori ZG. Syringecartridge solidphase extraction method for patulin in apple juice, J. AOAC Int. 86: 11601163 (2003) 23. Gaspar EMSM, Lucena AFF. Improved HPLC methodology for food controlfurfurals and patulin as markers of quality. Food Chem. 114: 15761582 (2009)