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Printed in the Republic of Korea "/"-:5*$"- 4$*&/$& 5&$)/0-0(: Vol. 26, No. 1, 19-26, 2013 http://dx.doi.org/10.5806/ast.2013.26.1.019 Analysis of gibberellic acid from fruits using HPLC/UV-vis Kyung Na Ma, Hyun-Woo Cho and Seung-Woon Myung Department of Chemistry, Kyonggi University San 94-6, Lui-dong, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-760, Korea (Received August 23, 2012; Revised December 10, 2012; Accepted December 19, 2012) )1-$67WJT w ùá x Á» w yw Abstracts: Gibberllic acid (GA 3 ) is one of gibberellins (GAs) that are a class of plant growth hormones that exert profound and diverse effects on plant growth and development. GA 3 is essentially non-uv absorbing and is difficult to assay by UV-detector. For effective extraction of gibberellic acid from fruits by using liquidliquid extraction, optimized ph and extraction solvent were established. The selective and sensitive derivative of GA 3 for HPLC/UV-vis was derivatized using phenacyl bromide, and the experimental factors, including reaction time, reaction temperature and amount of derivatizing reagent and base were investigated for the effective synthesis. The derivatized GA 3 with phenacyl bromide was effectively analyzed by HPLC/UV-vis. The structure of derivatized GA 3 was confirmed by HPLC/ESI-MS. For apple, LOD and LOQ were 0.008 mg/ kg and 0.027 mg/kg, respectively. For pear, LOD and LOQ were 0.003 mg/kg, 0.012 mg/kg, respectively. The established method can be applied to more effective analysis of GA 3 from plant and food. : Ÿ ƒ š (GAs) wù (GA 3 ) w» w w»ƒ. - w l z w» w ph w y wš w. rù y w» k ƒ GA 3 - yw, y y w» w, y,» y g x w. y GA 3 C18 f w w HPLC/UV-vis z, HPLC/ESI-MS w y yw y w., w (LOD) w (LOQ) ƒƒ 0.008 mg/kg, 0.027 mg/kg,, w (LOD) w (LOQ) ƒƒ 0.003 mg/kg, 0.012 mg/kg û w w. y y w GA 3 z š r w. Key words: gibberellic acid, plant hormone, HPLC/UV-vis, derivatization Corresponding author Phone : +82-(0)31-249-9647 Fax : +82-(0)31-249-9647 E-mail : swmyung@kgu.ac.kr 19

20 Kyung Na Ma, Hyun-Woo Cho and Seung-Woon Myung (Gibberellin) t y š wš j w w. w k š w 1, x j ³ w š. ù wš,,, y{ Ÿ w š, j» š g t w w. ƒ y»»» w w (Gibberllic acid, GA 3 ) w wš, ù w ³ ƒ. w MRL (Maximum Residue Limit) w 200 µg/kg ³ š, EU w 1 500 µg/kg ³. wr, xÿ š UV ƒ û p w yw», HPLC/UV-vis w 2 w w. 3-7 GC/MS ù 8-10 LC/MS 11-19,22 w w ƒ, capillary electrohoresis-ms w 20-21 w š. w, x š HPLC/UV-Vis w q 206 nm ûš Ÿ ƒ û» UV» w»». - (Liquidliquid extraction) w l z w,» q» w y rù (Phenacyl bromide) w 23-26» α-bromo-2-acetonaphthone y z š rw 27 y g Ÿ ƒ k HPLC/UV-Vis w z w y w. x» x», k, m 3 z w w. k yw w EYELA (Tokyo, Japan) MMS-3010 w š, w» Caliper Lifescience (Seattle, WA, USA) Turbo LV» w. t Sigma-Aldrich (St Louis, MO, USA) š w, yw Fig. 1 ùkü. THF (tetrahydrofuran), k, p l p, J.T.Baker (NJ, USA) HPLC w š, (formic acid) Fluka (Seelze, Germany), rù Sigma- Aldrich (St Louis, MO, USA) w.» UV-vis»ƒ Agilent (Palo Alto, CA, USA) 1100 series HPLC l w. LC/ESI-MS/MS Agilent (Palo Alto, CA, USA) 1200 series HPLC/6410 Triple Quadruple tandem mass spectrometer l w š, y» y(esi, Electrospray Ionization) w. kw q w 4 o C w þ w z x ³ y» ³ yw w. ³ y» ³ yw 5 g wš 10 ml ƒw z y : (1:1, v/v) w ph 3 w. p l p 20 ml ƒw k yw» 300 rpm 15 Fig. 1. Chemical structure of gibberellic aicd (GA 3 ). Analytical Science & Technology

Analysis of gibberellic acid from fruits using HPLC/UV-vis 21 Fig. 2. Scheme for derivatization of GA 3 with phenacyl bromide. k k z, 4000 rpm 5 z d p l p d w, 2z w. w p l p d yww z ph 8.0 (Phosphate buffer) 10 ml ƒ w. k yw» 300 rpm 15 k jš, 4000 rpm 5 w, d wš, y : (1:1, v/v) w ph 3.0 w. 10 ml p l p ƒwš kyw» 300 rpm 15 k k z, p l p d w 45 o C» { g k z THF 300 µl ƒw.» 5 µl p p ƒwš THF 0.2 M rù 40 µl ƒw. 2 vortex mixer yww, 90 o C 1 g (Fig. 2). k z x þƒ k z» w 40 o C g. k 100 µl z HPLC/ UV-Vis 10 µl w w, Fig. 3 y w.»» )1-$67WJT y w HPLC f Waters (Milford, Massachusetts, USA) SunFire C18 ¼ 150 mm, ü 4.6 mm š j» 5 µm. k w»»»» 60% 15 ¾ 70% ƒ 15.1 50% g 30 ¾ w, sx w 30.1 ¾» 60% g 10 w, Fig. 3. Sample preparation procedure of Gibberellic acid. 40. q 247 nm 0.8 ml/min, 10 µl. )1-$&4*.4 y y w HPLC/ESI-MS f Waters (Milford, Massachusetts, USA) XBridge C18 ¼ 100 mm, ü 2.1 mm š j» 3.5 µm. k š (50%» ) w, 0.3 ml/min, 15. HPLC/MS y ESI (Electrospray ionization), Vol. 26, No. 1, 2013

22 Kyung Na Ma, Hyun-Woo Cho and Seung-Woon Myung ( ) w. w w z š x z w w (Limit of detection, LOD), w (Limit of quantitiation, LOQ), z š w x k ( )ƒ., w w x w ƒƒ t ƒw e y (Signal to Noise, S/N) mw w w w z, w w 1~5 ƒ (n=7) w. HPLC/UV-vis z mw d w t r (σ) wš, x š w»»(s) w z w 3σ/s, w 10σ/s w. š w w w (t ) w sƒ. 0.15, 0.3, 0.4, 0.8, 1.6, 3.2 mg/kg t ƒw š, 0.15, 0.3, 0.45, 1.0, 2.0, 4.0 mg/kg t ƒw y e z HPLC/UV-vis w vj š wš, (r ) 2 w. š rp»» rp y w t q 206 nm, rù y k y GA 3 q 247 nm, w Ÿ Fig. 4. UV spectra of (a) GA 3 and (b) derivatized GA 3. Fig. 5. HPLC/UV-vis chromatogram of derivatized gibberellic acid. ƒ, rp Fig. 4 ùkü. )1-$677JT y HPLC/UV-Vis l w w. y g» w» y»» w y p w wz 27.26 j m Fig. 5 ùkü. )1-$&4*.4 y y w» w HPLC/ESI-MS w. y ƒ 1 (Pseudomolecular ion) [M-H] ƒ m/z 463 ùkû yƒ y w. r p Fig. 6 ùkü. Fig. 6. Mass spectrum of derivatized GA 3 with electrospray ionization. Analytical Science & Technology

Analysis of gibberellic acid from fruits using HPLC/UV-vis 23 x y y - w l z w» w ph y g x x w. 1) ph w» z» w ph w w v x w.,» yw xk» š xk», Henderson-Hasselbalch w l» w ü» w ph û w.» j» w y 1:1(v/v) y w ph w. ph 3 ƒ z ùkþ Fig. 7 ùkü. 2) w - z w» w p l p, p l, p j (MC) w kw. ƒ ƒ ƒ p l p z w w (Fig. 8). y y y z» w,, (THF),»(p p ), y (rù ) x y g ƒ y x w. 1) w y w k y j w e. rù y w» w w w. 40, 50, 60, 70, 80, 90 o C k z HPLC w 90 o C ƒ Fig. 9 ùkü. wr, 15, 30, 1~8 y g k 1 ƒ z y w (Fig. 10). 2) THF w y w w THF Fig. 7. Comparison of absolute recovery at various PHs. Fig. 9. Comparison of derivatized GA 3 according to reaction temperatures. Fig. 8. Comparison of absolute recovery by extraction solvents. Fig. 10. Comparison of derivatized GA 3 according to reaction times. Vol. 26, No. 1, 2013

24 Kyung Na Ma, Hyun-Woo Cho and Seung-Woon Myung Fig. 11. Effect of according to volume of tetrahydrofuran. w š, -COO H + y k w ù w. w w THF ƒƒ 200, 300, 500, 700, 1000 µl g HPLC vj w, ƒ ƒw y w 300 µl kw (Fig. 11). 3) rù w rù e (-COOH)» y k, rù»ƒ ƒ š q HPLC/UV-vis w w. THF 0.2 M rù w š ƒƒ 10, 20, 30, 40, 50 µl ƒw 40 µl HPLC v j ƒ j ùkû (Fig. 12). 4) p p w rù w z y w» w p p» w. w p p 2, 5, 8, 10, 20, 30 µl ƒw 30 µl Fig. 12. Effect of according to volume of phenacyl bromide. Fig. 13. Effect of according to volume of triethylamine. ƒw ƒ (Fig. 13). z w w y w y ƒ k (, ) t ƒ (spike)w z z w., w (LOD) w (LOQ) ƒƒ 0.008 mg/ kg, 0.027 mg/kg ùkû, 0.15 mg/kg~3.2 mg/ kg 88.1~105.9% z ùký y š, t r (RSD%) 1.0~4.6% yw w ù kü., w (LOD) w (LOQ) ƒ ƒ 0.003 mg/kg, 0.012 mg/kg ùkû, 0.15 mg/ kg~4.0 mg/kg 84.4~108.4% z ù ký y ƒ w. t r (RSD%) 1.0~3.8% w ùkü (Table 1). š 5 g ƒ 0.15, 0.3, 0.4, 0.8, 1.6, 3.2 mg/kg t ƒw z (n=3) HPLC/UV-vis w š w y=1950.6x+97.286 (r 2 =0.9973)., ƒ 5 g ƒ 0.15, 0.3, 0.45, 1.0, 2.0, 4.0 mg/kg t ƒw z (n=3) HPLC/UV-vis w š w y=1501.1x + 21.877 (r 2 =0.9963). Analytical Science & Technology

Analysis of gibberellic acid from fruits using HPLC/UV-vis 25 Table 1. LOD, LOQ, accuracy and precision for gibberellic acid from apple and pear Compound Gibberellic acid Matrices LOD * (mg/kg) LOQ ** (mg/kg) Apple 0.008 0.027 Pear 0.003 0.012 Conc. (mg/kg) RSD *** (%) (n=3) Accuracy *** (recovery%) (n=3) 0.15 1.8 97.8 0.3 1.0 88.1 0.4 4.6 88.9 0.8 1.4 105.7 1.6 2.5 105.9 3.2 4.0 98.4 0.15 1.5 84.4 0.3 1.2 86.2 0.45 3.0 91.1 1.0 3.8 102.0 2.0 1.0 108.4 4.0 1.0 97.9 *LOD(Limit of Detection)=3σ/s **LOQ(Limit of Quantitation)=10σ/s (σ=standard deviation, s=slop of calibration curve) ***Accuracy(%)=(measured value/spiked value) 100 ù wš, HPLC cut-off q q ùkù UV» rù w rw y mw y yw k HPLC/UV-vis w š z w y w. w LC/ESI-MS w y y w., w (LOD) w (LOQ) ƒƒ 0.008 mg/kg, 0.027 mg/kg,, w (LOD) w (LOQ) ƒƒ 0.003 mg/kg, 0.012 mg/kg û w w. z d w 88.1~105.9%, 84.4~108.4% ùkû. p t r (RSD%)ƒ 4.6% w ùk ý y x ùkü, w š ü r 2 =0.996 ùkü. rù w y HPLC/UV-vis w ù», š 1 ü mw 23-26 y w. w, y rù w HPLC/UV-vis» α-bromo-2- acetonaphthone w q HPLC/UV-vis w 27 w rwš, mw w û y ƒ š w. š x 1. W. Xie, C. Han, Z. Zheng, X. Chen, Y. Qian, H. Ding, L. Shi and C. Lv, Food Chem., 127, 890-892 (2011). 2. Z. Ma, L. Ge, A. S. Y. Lee, J. W. H. Yong, S. N. Tan and E. S. Ong, Anal. Chim, Acta., 610, 274-281 (2008). 3. S. W. Johnson and C. R. Coolbaugh, Plant Physiol., 94, 1696-1701 (1990). 4. P. Tansupo, P. Suwannasom, D. L. Luthria, S. Chanthai and C. Ruangviriyachai, Phytochem, Anal., 21, 157-162 (2010). 5. G. Castillo and S. Martinez, J. Chromatogr. A, 782, 137-139 (1997). 6. M. Kelen, E. C. Demiralay, S. Sen and G. Ozkan, Turk J Chem., 28, 603-610 (2004). 7. D. Weiss, A. Luit, E. Knegt, E. Vermeer, J. N. M. Mol and J. M. Kooter, Plant Physiol., 107, 695-702 (1995). Vol. 26, No. 1, 2013

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