B Y T TRNG I HC DC H NI PHM TH THU H M SINH VIấN: 1101139 NGHIấN CU PHNG PHP XC NH AURAMIN O TRONG THC N CHN NUễI BNG LC-MS/MS KHểA LUN TT NGHIP DC S H NI 2016 B Y T TRNG I HC DC H NI PHM TH THU H M SINH VIấN: 1101139 NGHIấN CU PHNG PHP XC NH AURAMIN O TRONG THC N CHN NUễI BNG LC-MS/MS KHểA LUN TT NGHIP DC S Ngi hng dn: TS Trn Cao Sn ThS ng Th Ngc Lan Ni thc hin: Vin Kim nghim an ton v sinh thc phm Quc gia H NI - 2016 www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com i LI CM N Sau thi gian thc hin ti vi nhiu n lc v c gng, thi im H N ti nhng ngi ó nhit tỡnh dy d, giỳp em thi gian qua N hon thnh khúa lun l lỳc em xin phộp c by t lũng bit n ca mỡnh Em xin chõn thnh cm n! H Ni, thỏng nm 2016 Sinh viờn Phm Th Thu H D I N N TO N -L - H ể A 10 00 B TR N H N G www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com O Em cng xin chõn thnh cm n ThS ng Th Ngc Lan ó nh hng cho em quỏ trỡnh tỡm ti liu cng nh gúp ý hon thnh khúa lun Em xin gi li cm n cỏc thy cụ b mụn Húa phõn tớch v c cht Trng i hc Dc H Ni, ban lónh o cựng ton th cỏn b nhõn viờn Vin Kim nghim an ton v sinh thc phm Quc gia ó to iu kin giỳp em sut thi gian nghiờn cu thc hin ti Cui cựng, vi tt c lũng bit n sõu nng em xin dnh cho gia ỡnh, bn bố ó chm súc, c v, ng viờn em sut quỏ trỡnh hc cng nh cuc sng Trong quỏ trỡnh thc hin ti, ó n lc v c gng ht sc nhng khụng trỏnh nhng thiu sút, em kớnh mong nhn c nhng ý kin ch bo v phờ bỡnh ca quý thy cụ Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ TP Q U Y Trc ht em xin by t lũng kớnh trng v bit n sõu sc ti TS Trn Cao Sn, ngi ó giao ti v tn tỡnh hng dn, giỳp em sut quỏ trỡnh thc hin v hon thnh khúa lun ny úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com ii MC LC ii H DANH MC CC K HIU, CC CH VIT TT v N MC LC LI CM N i U Y N DANH MC CC BNG .vi TP T VN O Chng TNG QUAN www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com 1.1 Tng quan v Auramin O N G 1.1.1.Khỏi quỏt chung H 1.1.2 Cu trỳc, tớnh cht húa lý TR N 1.1.3.c tớnh 1.1.4.Cỏc quy nh v hm lng ca Auramin O B 1.2 Tng quan phng phỏp xỏc nh Auramin O 10 00 1.2.1 Cỏc phng phỏp ó c thc hin xỏc nh Auramin O 1.2.2 Phng phỏp LC-MS/MS ể A 1.2.2.1 Sc kớ lng (HPLC) - H 1.2.2.2 Khi ph 10 -L Chng I TNG V PHNG PHP NGHIấN CU 13 N 2.1 i tng nghiờn cu 13 TO 2.2 Nguyờn vt liu trang thit b 13 Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ Q DANH MC CC HèNH V V TH .vii D I N N 2.2.1 Nguyờn vt liu 13 2.2.1.1 Cht chun 13 2.2.1.2 Hoỏ cht, dung mụi 13 2.2.2 Trang thit b 14 2.2.2.1 Thit b 14 2.2.2.2 Dng c 14 úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com iii 2.3 Ni dung nghiờn cu 14 2.3.2 Kho sỏt cỏc iu kin x lý mu 15 N 2.3.1 Kho sỏt cỏc iu kin xỏc nh cht mu AUO bng LC-MS/MS 15 H 2.3.3 Thm nh phng phỏp 15 U Y N 2.3.4 ng dng phng phỏp 15 TP 2.4.1 Phng phỏp ly mu 16 O 2.4.2 Phng phỏp x lý mu s b16 www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com 2.4.3 Phng phỏp chit pha rn.16 N G 2.4.4 Phng phỏp thm nh 18 H 2.4.4.1 Tớnh c hiu, chn lc 18 TR N 2.4.4.2 Gii hn phỏt hin, gii hn nh lng 18 2.4.4.3 Khong tuyn tớnh v ng chun 19 10 00 B 2.4.4.4 lp li v thu hi 19 2.4.5 Phng phỏp x lý s liu 20 A Chng THC NGHIM, KT QU V BN LUN 21 H ể 3.1 Ti u húa iu kin tỏch v xỏc nh AuO bng LC-MS/MS 21 -L - 3.1.1 Ti u húa cỏc iu kin ph 21 N 3.1.1.1 La chn ion phõn t v ion sn phm 21 TO 3.1.1.2 Ti u húa cỏc iu kin MS 22 D I N N 3.1.2 La chn cỏc iu kin sc kớ lng 23 Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ Q 2.4 Phng phỏp nghiờn cu 15 3.1.2.1 Chn pha tnh 23 3.1.2.2 Kho sỏt thnh phn pha ng 23 3.2 Kho sỏt cỏc iu kin x lý mu 25 3.2.1 Chn quy trỡnh x lý mu 25 3.2.2 Kho sỏt dung mụi chit 26 3.2.3 Kho sỏt ct chit pha rn SPE 28 úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com iv 3.2.4 Kho sỏt dung mụi gii 29 3.3.1 Tớnh c hiu, chn lc 31 N 3.3 Thm nh phng phỏp phõn tớch 31 H 3.3.2 Gii hn phỏt hin (LOD) v gii hn nh lng (LOQ) 32 U Y N 3.3.3 Khong tuyn tớnh v ng chun 34 TP 3.4 Kt qu xỏc nh AUO mt s mu TACN 38 O KT LUN V XUT 41 www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com Kt lun 41 N G Kin ngh 42 D I N N TO N -L - H ể A 10 00 B TR N PH LC H TI LIU THAM KHO Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ Q 3.3.4 lp li v thu hi 36 úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com v DANH MC Kí HIU, CH VIT TT Amoni acetat AF Formic acid Acid formic AUO Auramine O Auramin O (vng ụ) Association of Official Hiu hi cỏc cng ng Analytical Communities phõn tớch chớnh thc Atmospheric pressure chemical Ch ion húa húa hc ionization ỏp sut khớ quyn CAV Cell Accelerator Voltage Th gia tc mng CE Collision Energy ESI Electronspray ionization FLD Fluoroscence detector H N U Y TP Q B 10 00 Balance High performance liquid A HPLC O G N TR N H Nng lng va chm Hydrophilic lipophilic HLB N Amonium acetate APCI Ion húa phun in t Detector hunh quang Cõn bng a nc- a bộo Sc ký lng hiu nng cao H ể chromatography Liquid chromatography tandem Sc ký lng ghộp ph - LC-MS/MS ln LOD Limit of detection Gii hn phỏt hin LOQ Limit of quantification Gii hn nh lng MS Mass spectrometry Khi ph R(%) Recovery Hiu sut thu hi RSD Relative Standard Deviation lch chun tng i SCX Strong Cation eXchange Trao i cation mnh SD Standard Deviation lch chun SPE Solid phase extraction Chit pha rn TO N -L mass spectrometry N I N D Ting vit AA AOAC www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com Ting anh úng gúp PDF bi GV Nguyn Thanh Tỳ Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ Ký hiu www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com vi Thin Layer Chromatography Sc kớ lp mng WAX Weak Anion eXchange Trao i anion yu Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ D I N N TO N -L - H ể A 10 00 B TR N H N G www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com O TP Q U Y N H TLC N Thc n chn nuụi TACN úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com vii DANH MC BNG Bng 1.2 Mt s phng phỏp xỏc nh v nh lng Auramin O cỏc N Bng 1.1 Giỏ tr gii hn quc t ca Auramin nm 2007 N H nn mu khỏc Q LC-MS hoc LC-MS/MS TP Bng 2.1 S im IP cho cỏc k thut phõn tớch 18 www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com O Bng 3.1 Cỏc iu kin phõn tớch AUO bng ESI(+)-MS/MS 21 G Bng 3.2 Cỏc thụng s ti u ca MS i vi ch ion dng 23 H N Bng 3.3 Chng trỡnh gradient phõn tớch Auramin O 24 Bng 3.4 So sỏnh cỏc loi dung mụi chit n din tớch pic ca AUO 27 TR N Bng 3.5 Kho sỏt ct SPE n thu hi ca AUO 28 Bng 3.6 Kho sỏt t l dung mụi gii 30 10 00 B Bng 3.7 S ph thuc gia din tớch pớc v nng dung mụi 35 Bng 3.8 S ph thuc gia din tớch pớc v nng nn mu.35 ể A Bng 3.9 lp li v thu hi ca AUO trờn nn mu TACN 37 - H Bng 3.10 Kt qu xỏc nh hm lng AUO mt s mu TACN ti H D I N N TO N -L Ni 39 Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ U Y Bng 1.3 Mt s phng phỏp xỏc nh Auramin O thc phm bng úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com viii H Hỡnh 1.1 Cụng thc cu to ca Auramin O N DANH MC HèNH V N Hỡnh 1.2 Mụ hỡnh h thng LC-MS/MS 11 TP Hỡnh 3.2 Sc kớ dung dch chun AUO 50 ng/mL phõn tớch bi cỏc h O gradient 25 www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com Hỡnh 3.3 Quy trỡnh x lý mu kho sỏt 26 N G Hỡnh 3.4 Sc ký AUO s dng cỏc dung mụi chit khỏc 27 H Hỡnh 3.5 Kho sỏt cỏc loi ct SPE 29 TR N Hỡnh 3.6 Quy trỡnh x lý mu ti u 31 Hỡnh 3.7 Sc pic AUO mu thờm chun, mu chun v mu trng 32 B Hỡnh 3.8 Sc AUO ti LOD 0,2 ng/mL ( tng ng àg/kg trờn mu) 10 00 33 Hỡnh 3.9 Sc AUO ti LOQ 0,5 ng/mL ( tng ng 20 àg/kg trờn mu) ể A 33 - H Hỡnh 3.10 ng chun AUO dung mụi 36 -L Hỡnh 3.11 ng chun AUO nnmu 36 D I N N TO N Hỡnh 3.12 Sc phõn tớch lp li mu AUO nng 25 ng/mL38 Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ Q U Y Hỡnh 3.1 Sc cỏc ion sn phm.22 úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com - Hỡnh 3.12 Sc phõn tớch lp li mu AuO nng 25 ng/mL -L Vi cỏc kt qu thm nh, cho thy phng phỏp cú tin cy, TO N nhy v chớnh xỏc ỏp ng c cỏc yờu cu cú th ng dng phõn tớch AuO cỏc nn mu l TACN Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ H ể A 10 00 B TR N H N G www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com O TP Q U Y N H N 38 D I N N 3.4 Kt qu xỏc nh AUO mt s mu TACN Trờn c s phng phỏp ó xõy dng, chỳng tụi tin hnh xỏc nh hm lng AUO trờn cỏc mu TACN c ly trờn th trng H Ni Cỏc kt qu c tng hp bng 3.10 úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com 39 a im ly mu Kt qu M-01 Qun Hong Mai KPH M-03 O 79,7 àg/kg 22,8 àg/kg Qun T Liờm 198 àg/kg M-07 KPH H M-06 TR N N G M-05 KPH 10 00 B M-08 M-09 ể H - M-11 N TO N -L M-12 KPH KPH A M-10 I N D N TP KPH Qun Long Biờn KPH 1385 àg/kg M-13 KPH M-14 180 àg/kg M-15 163 àg/kg Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ KPH Q U Y M-02 M-04 www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com H Kớ hiu N Bng 3.10 Kt qu xỏc nh hm lng AUO mt s mu TACN ti H Ni Nhn xột: Theo kt qu bng 3.10 phỏt hin c 6/15 mu cú cha AUO hm lng t 79,7 -1385 g/kg ú mu M-12 cú hm lng AUO cao gn 1,4 mg/kg Hm lng ny cao hn ngng gii hn theo quy úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com 40 nh ca b NN&PTNT TACN l mg/kg Do s lng mu cũn ớt nờn cha th ỏnh giỏ xỏc thc v tỡnh trng s dng AUO TACN trờn a Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ D I N N TO N -L - H ể A 10 00 B TR N H N G www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com O TP Q U Y N H N bn H Ni úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com 41 Q - Tỏch bng sc ký lng pha o s dng ct C18 TP - Phõn tớch bng MS/MS vi ngun ESI(+), ch MRM O - Chn c chng trỡnh gradient: kờnh A (ACN), kờnh B (HCOOH www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com 0,1%) nh bng 3.3 N G - Tc dũng 0,5 ml/phỳt H ó kho sỏt v la chn c iu kin chit AUO TACN, c th TR N nh sau: - Dung mụi chit: Methanol B - Lm sch bng ct SPE C18: 10 00 Ra gii bng dung mụi methanol A Ra bng dung mụi methanol : H2O (20 : 80) H ể - Quy trỡnh x lý mu nh hỡnh 3.6 -L nh sau: - ó thm nh phng phỏp phõn tớch AUO TACN vi cỏc kt qu N - Phng phỏp cú tớnh chn lc ỏp ng yờu cu; AUO c la chn TO ba ion, mt ion c s dng nh lng v hai ion dựng khng nh s Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ U Y N TACN, c th nh sau: H Kt lun ó kho sỏt v la chn c iu kin LC-MS/MS phõn tớch AUO N KT LUN V XUT D I N N cú mt ca AUO - Khong tuyn tớnh khong nng t 0,5 ng/mL n 50 ng/mL - Gii hn nh lng ca AUO TACN t 20 àg/kg, gii hn phỏt hin t àg/kg - lp li v thu hi ca phng phỏp tt Hiu sut thu hi t 82,4 n 109,2 % úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com 42 ó s b ỏnh giỏ hm lng AUO trờn mt s mõu TACN H Ni vi kt qu 6/15 mu dng tớnh ú cú mu cú hm lng AUO cao hn N gii hn cho phộp TACN H Kin ngh Q da mui TP - Xõy dng quy trỡnh xỏc nh c ng thi cỏc nhúm cht mu D I N N TO N -L - H ể A 10 00 B TR N H N G www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com O tng t Auramin O thc phm nh Rhodamin, chrysoidin Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ U Y N - M rng thờm i tng phõn tớch thc phm nh tht g, mng, úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com TI LIU THAM KHO Ting Vit N Trn T An (2007), Húa phõn tớch 2, Trng i hc Dc H N B NN&PTNT (2015), "Thụng t ban hnh danh mc b sung húa U Y H Ni .Q cht, khỏng sinh cm nhp khu, sn xut, kinh doanh v s dng TP thc n chn nuụi gia sỳc, gia cm ti Vit Nam", 42/2015/TT- O B NN&PTNT, Cc Chn nuụi (2015), "Quyt nh v vic m rng G www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com BNNPTNT H N phm vi ch nh phũng th nghim thc n chn nuụi gia sỳc, gia cm", Q 846/TACN Nguyn Minh c (2006), Sc kớ lng hiu nng cao v mt s ng TR N 10 00 nhiờn, NXB Y hc A Ting Anh ể Allison R., Garratt N (1989), "Solvent systems for thin layer H B dng v nghiờn cu, kim nghim dc phm, dc liu v hp cht t - chromatography of biological dyes", Medical laboratory sciences, -L 46(2), pp 113-119 Ardrey R E (2003), Liquid chromatography-mass spectrometry: an N TO introduction, John Wiley & Sons I N N Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ Bonser G M., Clayson D B., Jull J W (1956), "The induction of tumours of the subcutaneous tissues, liver and intestine in the mouse by certain dyestuffs and their intermediates", British journal of cancer, D 10(4), p 653 Case R., Hosker M E., Mcdonald D B., et al (1954), "Tumours of the urinary bladder in workmen engaged in the manufacture and use of úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com certain dyestuff intermediates in the British chemical industry Part II Further consideration of the role of aniline and of the manufacture of N auramine and magenta (fucshine) as possible causetive agents.", British N European Concil (1994), European parliament and concil derective European Commission (2004), Commission Directive 2004/93/EC of TP 10 .Q 94/36/EC on colors for use in foodstuffs O 21 September 2004 amending Council Directive 76/768/EEC for the N European Commission (2004), Directive 2004/37/EC of the European H 12 G www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com purpose of adapting its Annexes II and III to technical progress Parliament and of the Council of 29 April 2004 on the protection of TR N workers from the risks related to exposure to carcinogens or mutagens European Communities (2002), The performance of Analytical 10 00 12 B at work ể Gessner T., Mayer U (2000), "Triarylmethane and diarylmethane H 13 A Methods and interpretation of results, (2002-657-EC) Gestis (2007), "International limit values for chemical agents and N 14 -L - dyes", Ullmann's encyclopedia of industrial chemistry TO Health", BG Institute for Occupational Safety and Health D I N N 15 16 Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ U Y H journal of industrial medicine, 11(2), pp 213-216 Green F J (1990), The Sigma-Aldrich handbook of stains, dyes and indicators, Aldrich Chemical Co Huang Ya-Pei W G.-F., Xia Kun,Wang Jiao-Qing,Cao Xu-Ni (2013), "Determination of chrysoidin II and auramine O in fish via high performance liquid chromatography", Chemical reagents, 26, pp 1730 úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn 17 www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com Hui-Lan (2014), "Detemination of chrysoidin,auramine O,astrazon orange G and astrazon orange residue in chillies by solid phase N extraction-high performance liquid chromatography-tandem mass N H spectrometry", Chinese Journal of analysis Labotarory, 33, pp 100- www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com Toxicology and occupational health", N Lide D (2008), "Handbook of Chemistry and Physics", CRC Press, 88, TR N pp 3-30 21 Sozialmed H 20 Arbeitsmed G Prọventivmed, 13, pp 1-28 O Kirsch P., Fleig I., Frentzel-Beyme R., et al (1978), "Auramine 19 TP Risks to Humans", 99, pp 111-140 Lin S., Tu H., Sun L., et al (2011), "Simultaneous determination of with tandem mass 10 00 coupled B five yellow dyes in foods by high performance liquid chromatography spectrometry",Chinese journal of ể Meizhong L (2005), "Determination of auramine O in legume-food by H 22 A chromatography/Zhongguo hua xue hui, 29(1), pp 79-82 - high per-formance liquid chromatography-diode array detector", -L Science and Technology of Food Industry, 8, p 059 Parodi S., Santi L., Russo P., et al (1982), "DNA damage induced by N 23 D I N N TO auramine O in liver, kidney, and bone marrow of rats and mice, and in Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ IARC (2010), "IARC Monographs on the Evaluation of Carcinogenic Q 18 U Y 104 a human cell line (alkaline elution assay and SCE induction)", Journal of Toxicology and Environmental Health, Part A Current Issues, 9(56), pp 941-952 24 Rao P., Bhat R V (2003), "A comparative study on the synthetic food colours usage in foods procured from urban and rural areas of Hyderabad", Nutrition & Food Science, 33(5), pp 230-234 úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn 25 www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com Silver H., Sonnenwirth A., Alex N (1966), "Modifications in the fluorescence microscopy technique as applied to identification of acid- N fast bacilli in tissue and bacteriological material", Journal of clinical N Tan Enling X J (2012), "Determination of Basic Orange Acid U Y 26 H pathology, 19(6), pp 583-588 Tatebe C., Zhong X., Ohtsuki T., et al (2014), "A simple and rapid O www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com 27 TP Industry, 18, pp 27-31 G chromatographic method to determine unauthorized basic colorants H N (rhodamine B, auramine O, and pararosaniline) in processed foods", Food science & nutrition, 2(5), pp 547-556 Thetford D (2000), "Triphenylmethane and related dyes", Kirk-Othmer TR N 28 Encyclopedia of Chemical Technology B Tonogai Y., Kingkate A., Halilamian C (1983), "Quantitative 10 00 29 Determination of Colorants in Dried Shrimp and Shrimp Paste Using Extraction and High Performance Liquid A lon-Exchange - Tripathi M., Khanna S K., Das M (2007), "Surveillance on use of -L 30 H ể Chromatography", Journal of Food Protectionđ, 46(7), pp 592-595 N synthetic colours in eatables vis a vis Prevention of Food Adulteration TO Act of India", Food Control, 18(3), pp 211-219 D I N N 31 32 Von Mỹller A (1933), "Bladder alterations due to amines Experiences Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ Q Orange and Auramine O in Bean Products", Guangdong Chemistry from the industrial district of Basel (Ger.)", Z Urol Chir (Gynaekol), 36, pp 202-219 Wang J.-W., Zhong H.-J., Liang C.-Q (2010), "Determimation of Chrysoidin and Auramine O in Food by Solid Phase Extraction-Ultra Performance Liquid Chromatography-Mass Spectrometry", Analysis and Testing Technology and Instruments, 2, p 013 úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com PH LC Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - 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Ch qun ti nguyờn : Nguyn Thanh Tỳ www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com O TP Q U Y N H N www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com 10 00 B TR N H N G gii bng MeOH D I N N TO N -L - H ể A Ph lc Sc mu thc t Mu phỏt hin AuO Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - Ch qun ti nguyờn : Nguyn Thanh Tỳ O www.daykemquynhon.ucoz.com MailBox : nguyenthanhtuteacher@hotmail.com TP Q U Y N H N www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn úng gúp PDF bi GV Nguyn Thanh Tỳ www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DyKốmQuyNhn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com Mu Mu 12 TO N -L - H ể A 10 00 B TR N H Mu Mu 15 D I N N Mu 14 Mu khụng phỏt hin AuO Din n h tr giỏo dc : /C 1000B Trn Hng o Tp Quy Nhn Ngi sỏng lp : Nguyn Thanh Tun - 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Nghiên cứu phƣơng pháp xác định Auramin O thức ăn chăn nuôi LC- MS/MS” với mục tiêu sau: Xây dựng thẩm định phƣơng pháp xác định Auramin O thức ăn chăn nuôi LC- MS/MS Áp dụng phƣơng pháp để xác. .. www.facebook.com/daykemquynhonofficial www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DạyKèmQuyNhơn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com... www.facebook.com/boiduonghoahocquynhonofficial www.twitter.com/daykemquynhon https://plus.google.com/+DạyKèmQuyNhơn www.facebook.com/daykem.quynhon www.daykemquynhon.blogspot.com nghiên cứu ung