Phát triển phương pháp phân tích xác định đồng thời esomeprazole và naproxen trong thuốc bằng phương pháp hplc uv

IăH CăQU CăGIAăTP.ăHCM TR NG I H C BÁCH KHOA HU NHăTH ăXUÂNăTRANG PHÁT TRI N PH NG PHÁP PHỂN TệCH XÁC NH NG TH I ESOMEPRAZOLE VÀ NAPROXEN TRONG THU C B NG PH NG PHÁP HPLC-UV Chuyênăngành:ăK ăThu tăHóaăH că Mã s :ă8520301 LU NăV NăTH CăS TP.ăH ăCHÍăMINH,ăthángă07 n mă2022ă Cơngătrìnhăđ căhồnă thànhăt i:ă Tr ng i H c Bách Khoa ậ HQG ậ HCM Cánăb ăh ngăd năkhoaăh c: TS.ăTr năTh ăKi uăAnh Cánăb ăch mănh năxétă1:ăTS.ă inhăV năPhúc Cánăb ăch mănh năxétă2:ăTS.ăTr năPh Lu năv năth căs ăđ căb oăv ăt iăTr căNh tăUyên ngă iăh căBáchăKhoa,ă HQGăTp.ăHCMă ngàyă28ăăthángă07ăn mă2022 Thànhăph năH iăđ ngăđánhăgiáălu năv năth căs ăg m: Ch ăt ch:ăPGS.ăTSăNguy năQuangăLong Th ăkỦ:ăTS.ă ngăB oăTrung Ph năbi nă1:ăTS.ă inhăV năPhúc Ph năbi nă2:ăTS.ăTr năPh căNh tăUyên yăviên:ăTS.ăTr năTh ăKi uăAnh Xácănh năc aăCh ăt chăH iăđ ngăđánhăgiáăLVăvàăTr ngànhăsauăkhiălu năv năđãăđ CH T CH H I NG ngăKhoaăqu nălỦăchuyên căs aăch aă(n uăcó) TR NG KHOA K THU T HĨA H C C NG HỊA Xẩ H I CH NGH A VI T NAM IăH CăQU CăGIAăTP.HCM TR NG I H C BÁCH KHOA c l p ậ T ậ H nh phúc NHI M V LU N V N TH C S H ătênăh căviên: Hu nhăTh ăXuânăTrang MSHV: 1970653 Ngày,ătháng,ăn măsinh:ă03/04/1993 N iăsinh:ăTp.ăHCM Chuyênăngành:ăK ăThu tăHóaăh c Mãăs :ă8520301 I TÊN TÀI: Ti ng Vi t:ă“Phátătri năph ngăphápăphânătíchăxácăđ nhăđ ng th i esomeprazole naproxen thu c b ngăph ng pháp HPLC-UV”ă Ti ng Anh:ă“Development of a rapid and simple analytical method for simultaneous determination of esomeprazole and naproxen in binary combination by HPLC ậ UV” NHI M V VÀ N I DUNG  Kh o sát quy trình chu n b m u cho q trình phân tích  Kh oăsátăđi u ki n s c ký  Th măđ nh quy trình phân tích  ng d ng quy trình v a phát tri n phân tích m t s m u thành ph m II NGÀY GIAO NHI M V : 22/02/21 III NGÀY HOÀN THÀNH NHI M V : 06/06/22 IV CÁN B H NG D N: TS Tr n Th Ki u Anh Tp HCM, ngày CÁN B H NG D N TR CH NHI M B tháng MỌN ÀO T O NG KHOA K THU T HÓA H C i n m 20 L I CÁM Sau m t th i gian h c t p nghiên c uăd N i s đ nhăh ng d n d t c a cô TS Tr n Th Ki u Anh, lu năv năth căs ăv iăđ tài:ă“Phátătri năph ngăphápăphânătíchă xácăđ nhăđ ng th i Esomeprazole Naproxen thu c b ngăph UV”ăđãăđ ngăphápăHPLC- c th c hi n hồn thành Tơi xin bày t lịng bi tă năsâuăs c t i: TS Tr n Th Ki uăAnh,ăng iăcơăđãăt nătìnhăh ng d n,ăgiúpăđ cho tơi nh ng ki n th căquỦăbáuăđ tơi hồn thành lu năv n.ă BanăLãnhăđ o Khoa K thu t Hoá h c Ban Giám Hi uăTr ngă HăBáchăKhoaă Tp.ăHCMăđãăt oăđi u ki n thu n l i cho tham gia h c t p hoàn thành lu năv nă đúngăth iăgianăquyăđ nh CN Nguy n H u Gia B o,ăDS.ăVõăThanhăS n,ăDS.ăHàăThanhăTúăvà b n t i B ph n R&D - Trung tâm Ngiên c u Phát tri n Công ngh cao thu căCôngătyăCPăD c ph măSaViPharmăđãăgiúpăđ trình h c t p nghiên c u t i công ty DS Thái Hi năL ng,ăng iăemăvàăc ngălàăng iăđ ng nghi păđãăđ ngăviên,ăgiúpăđ chia s v i nh ngăkhóăkh nătrongăcơngăvi c tơi th c hi n lu năv n.ă Và cu i cùng, xin chân thành c mă năgiaăđình,ăb năbèăđãăquanătâmăđ ng viên tơi trình h c t p th c hi n lu năv n Tp HCM, ngày tháng n m 20 H căviên HU NH TH ăXUÂNăTRANG ii TịM T T LU N V N Esomeprazole (ESP) m t h p ch t có tác d ng c ch ti t axit d dày, h tr u tr b nhătràoăng c d dày th c qu n hi u qu Naproxen (NPX) có ho t tính ch ng viêmăkhôngăsteroid,ăth ngăđ c s d ngăđ gi m nhi u lo iăđau,ăs t, viêm Ngày nay, có nhi uăcôngătyăd c ph măđi u ch k t h p NPX ESP v i li uăl Vì v y, m c tiêu c a nghiên c u phát tri n m tăph ng khác ngăphápăphânătíchă nhanhăchóng,ăđángătinăc y,ăchínhăxácăvàăđ năgi năđ xácăđ nhăđ ng th i đ nh tính đ nhă l ng NPX ESP bào ch d c ph m S phână táchă đ tă đ ct c t HPLCăC8ă(150mmăxă4,6ămm,ă5ăµm),ăphaăđ ng s d ng g m Acetonitrile - đ m pH 7,6 có b sung ch t b t c p ion theo t l 30:70 (v/v), v i t căđ dòng 1,0 ml / phút, b c sóng phân tích 8,949 phút.ăPh t 230 nm Th iăgianăl uăc a NPX ESP l năl ngăphápăchoăth yăđ n tính c aăđ t 6,950 ng chu n v i giá tr h s ngăquanăr2 =ă0,9999ăđ i v i NPX ESP Hi u su t thu h i c a c hai lo iăd ch t n m gi i h n t 98%ăđ n 102%, ch ng t đ đúngăc aăph Các nghiên c u v đ chínhăxácăvàăđ xác trung gian c aăph ngăphápănày.ă ngăphápăm i có đ l ch chu năt ngăđ i (RSD) th păh nă2,0%,ăđ t u c uătheoăcácăh ICH.ăDoăđó,ăph ngăphápăHPLCă- UV thích h păđ xácăđ nhăhàmăl ESP thu c có th đ c áp d ngătrongăphânătíchăthơngăth NPX ESP cơng th căd c ph m iii c ng d n c a ng c a NPX ngăđ xácăđ nh ABSTRACT Esomeprazole (ESP) is a compound that inhibits gastric acid secretion and effective in the treatment of gastric oesophageal reflux diseases Naproxen (NPX) has non steroidal anti-inflammatory activity, which is commonly used for relief of a wide variety of pain, fever, inflammations Nowadays, there are many pharmaceutical companies prepare NPX and ESP combinations in different dosage strengths Thus, the objective of this study was to develop a rapid, reliable, reproducible, precise and simple analytical method for qualitative and quantitative simultaneous determination of NPX and ESP in pharmaceutical preparation The separation was achieved from HPLC Column C8 (150 mm x 4.6 mm, µm), Acetonitrile - buffer pH 7,6 with the addition of ion pair reagents in the ratio of 30:70 (v/v) as the mobile phase, at a flow rate of 1.0 ml/min with UV detection at 230 nm The retention time of NPX and ESP was found to be 6,950 and 8,949 minutes The method showed linear response with a correlation coefficient value r2= 0,9999 for NPX and ESP The recovery for both drugs was found between 98% and 102% which demonstrated the accuracy of this method Intra- and intermediate precision studies of the studied method were less than 2,0 % relative standard deviation (RSD) according to ICH guidlines Therefore, the RP - HPLC method is suitable for determining the concentration of NPX and ESP in tablets and it can applied for routine analysis for determination of the NPX and ESP in pharmaceutical formulations iv C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an L I CAM OAN Tơiăxinăcamăđoanăđâyălàăcơngătrìnhănghiênăc u c a riêng tơi, s li u k t qu đ c nêu lu năv nălàătrungăth căvàăch aăt ngăđ c công b b t kì cơng trình nghiên c u khác HU NH TH XUÂN TRANG Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn v C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an M CL C DANH M C VI T T T VIII DANH M C B NG BI U X DANH M C HÌNH V XII U M M C TIÊU C A CH TÀI NG 1: T NG QUAN IC 1.1 NG V NAPROXEN 1.1.1 Gi i thi u chung 1.1.2 C u trúc tính ch t c a Naproxen 1.1.3 Tác d ng d IC 1.2 c lý c a Naproxen NG V ESOMEPRAZOLE 1.2.1 Gi i thi u chung 1.2.2 C u trúc tính ch t c a Esomeprazole 1.2.3 Tác d ng d c lý c a Esomeprazole 1.3 T NG QUAN V PH KI N NG PHÁP QUANG PH T NGO I KH 1.4 T NG QUAN V PH NG PHÁP S C KÝ L NG HI U N NG CAO 1.4.1 Khái ni m 1.4.2 Phân lo i 1.4.3 Pha t nh s c ḱ pha đ o 10 1.4.4 H th ng máy HPLC 13 1.5 M T S PH NG PHÁP PHÂN TÍCH NPX VÀ ESP 15 1.6 T NG QUAN V K THU T S C KÍ PHA 1.7 T NG QUAN V H NG NGHIÊN C U 20 1.8 T NG QUAN TH M CH NG 2: 2.1 2.1.1 IT IT O GHÉP C P ION 18 NH QUY TRÌNH PHÂN TÍCH 21 NG VÀ PH NG PHÁP NGHIÊN C U 29 NG NGHIÊN C U 29 it ng nghiên c u nguyên li u 29 2.1.2 Dung mơi - Hố ch t: 29 2.1.3 Thi t b - D ng c 30 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn vi C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an 2.1.4 2.2 PH Chu n b hóa ch t – Ch t chu n 30 NG PHÁP NGHIÊN C U 31 2.2.1 Ki m tra đ tinh t c a chu n 31 2.2.2 Quy trình đ nh l 2.2.3 Kh o sát u ki n s c ký 32 2.2.4 Kh o sát quy trình chu n b m u 32 2.2.5 ng NPX ESP thu c viên ban đ u 31 ng d ng quy trình đ nh l ng 33 2.3 QUY TRÌNH X LÝ M U 33 CH NG 3: TH C NGHI M VÀ K T QU 34 3.1 KH O SÁT I U KI N S C KÝ 34 3.1.1 Kh o sát b 3.1.2 Kh o sát c t s c ký 36 3.1.3 Kh o sát pha đ ng 38 3.1.4 Kh o sát th tích tiêm m u 42 3.1.5 Kh o sát t c đ dòng 44 c sóng 34 3.2 CH N I U KI N S C KÝ 45 3.3 ÁNH GIÁ PH 3.2.1 Tính t NG PHÁP PHÂN TÍCH 48 ng thích h th ng 48 3.2.2 đ c hi u 49 3.2.3 Tính n tính 51 3.2.4 xác 53 3.2.5 55 3.4 CH NG D NG QUY TRÌNH PHÂN TÍCH TRÊN M U TH T 56 NG 4: K T LU N VÀ NGH 58 4.1 K T LU N 58 4.2 NGH 58 TÀI LI U THAM KH O 59 DANH M C PH L C 63 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn vii C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an DANH M C VI T T T STT CH VI T T T TI NG ANH TI NG VI T 1-HSA 1-Heptanesulfonate sodium APIs Active Pharmaceutical Ingredients ESP Esomeprazole FDA Food and Drug C ăquanăqu n lý Administration D D c ch t c ph m Th c ph m HPLC High-Performance S c ký l ng hi u Liquid n ngăcao Chromatography ICH International Council H iăđ ng qu c t v for Harmonisation s đ ng thu n IPC Ion ậ pair chromatography S c ký ghép c p ion k Capacity Factor H s dungăl KNV 10 LOD Limit of Detection Gi i h n phát hi n 11 LOQ Limit of Quantitation Gi i h năđ nhăl 12 NPX Naproxen 13 NSAID Non-steroidal antiinflammatory drug ng Ki m nghi m viên Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn viii ng Thu c ch ng viêm không steroid C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Ph l c 0.5 S c ký đ Th m đ nh đ l p l i Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 74 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an 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77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 76 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Ph l c 0.6 S c ký đ Th m đ nh đ xác trung gian Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 77 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 78 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 79 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 80 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 81 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 82 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Ph l c 0.7 S c ký đ m u th 375 - 20 NPX = 75 ppm ESP = ppm NPX = 75 ppm ESP = ppm Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 83 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Ph l c 0.8 S c ký đ m u th 500 - 20 NPX = 100 ppm ESP = ppm NPX = 100 ppm ESP = ppm Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 84 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Ph l c 0.9 S c ký đ m u th vi h t 20 mg ESP = ppm ESP = ppm Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 85 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Ph l c 0.10 S c ký đ m u th vi h t 40 mg ESP = ppm ESP = ppm Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 86 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Ph l c 0.11 S d ng cơng c ANOVA tính h s t ng quan n tính R cho đ ng chu n ESP NPX SUMMARY OUTPUT Regression Statistics Multiple R 0,999961545 R Square 0,999923091 Adjusted R Square 0,999903864 Standard Error 2509,532691 Observations ESP ANOVA df SS 3,2752E+11 25191017,3 3,27545E+11 MS Coefficients Standard Error -658,9509804 2003,315955 26451633,44 115991,5956 t Stat Regression Residual Total Intercept X Variable 1 H ăs ăt ngăquanătuy nătínhăRă= 3,2752E+11 6297754,326 -0,328930131 228,0478452 F Significance F 52005,8197 2,21815E-09 P-value 0,758709638 2,21815E-09 Lower 95% Upper 95% Lower 095% Upper 095% -6221,047758 4903,145797 -6221,04776 4903,1458 26129589,14 26773677,73 26129589,14 26773677,7 0,99996 SUMMARY OUTPUT Regression Statistics Multiple R 0,999972569 R Square 0,999945139 Adjusted R Square 0,999931424 Standard Error 77222,82035 Observations NPX ANOVA df SS 4,34778E+14 23853455932 4,34802E+14 MS Coefficients Standard Error 32554,98039 61645,62377 195978980,8 725807,4016 t Stat Regression Residual Total Intercept X Variable 1 H ăs ăt ngăquanătuy nătínhăRă= 4,34778E+14 5963363983 0,528098807 270,0151312 F Significance F 72908,17109 1,12865E-09 P-value 0,625370894 1,12865E-09 0,99997 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn 87 Lower 95% Upper 95% Lower 095% Upper 095% -138600,71 203710,6708 -138600,71 203710,671 193963816,4 197994145,2 193963816,4 197994145 C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn