本文選題：磁性材料　切入點(diǎn)：四環(huán)素類抗生素　出處：《中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院》2017年碩士論文

【摘要】：近年來功能化磁性微球作為一種新型固相萃取材料獲得越來越廣泛的關(guān)注。通過對(duì)微球表面進(jìn)行改性或修飾,可滿足污染物在提取、分離和凈化等多方面的需求。本研究利用不同功能化磁性材料對(duì)四環(huán)素類(四環(huán)素、土霉素、金霉素、強(qiáng)力霉素)、喹喏酮類(培氟沙星、諾氟沙星、氟羅沙星、左氧氟沙星、依諾沙星、洛美沙星、二氟沙星、司帕沙星、達(dá)氟沙星、環(huán)丙沙星、恩諾沙星、加替沙星)抗生素的吸附特性,建立了基于磁分散固相萃取的多種抗生素色譜質(zhì)譜檢測(cè)新技術(shù),相關(guān)研究對(duì)于進(jìn)一步探索和完善抗生素高靈敏度檢測(cè)新技術(shù),拓寬磁性材料的應(yīng)用范圍都具有重要的意義。主要的研究?jī)?nèi)容包括:1.基于氨基功能化磁性微球的四環(huán)素類抗生素HPLC檢測(cè)新技術(shù)本研究以Fe_3O_4為磁性內(nèi)核,制備了氨基修飾磁性功能材料,考察了不同材料對(duì)TCs的吸附性能。利用氨基功能化磁性微球(MNP-NH2)在有機(jī)相中對(duì)四環(huán)素類抗生素(TCs)高效的吸附特性,將分散固相萃取技術(shù)與磁固相萃取技術(shù)相結(jié)合,建立了4種TCs的磁分散固相萃取HPLC檢測(cè)新技術(shù),并應(yīng)用于牛奶樣品的檢測(cè)。內(nèi)容包括:(1)功能化磁性材料的制備:在實(shí)驗(yàn)室前期氨基修飾磁性微球基礎(chǔ)上,將SBA-15大分子介孔材料引入磁性功能材料制備,并進(jìn)一步優(yōu)化了APTES用量,研究制備了不同比表面積及氨基含量的磁性材料Fe_3O_4@SBA-15@APTES和Fe_3O_4@SiO_2@APTES。傅里葉紅外光譜,元素分析表征結(jié)果證實(shí)偶聯(lián)成功,對(duì)硝基苯甲醛比色法對(duì)磁性材料表面氨基定量結(jié)果表明:通過控制合成過程中APTES用量可制備不同氨基含量的磁性功能材料。(2)功能化磁性材料對(duì)TCs吸附效果研究:Fe_3O_4@SiO_2@APTES在乙腈溶液中對(duì)TCs展示了良好的吸附特性。實(shí)驗(yàn)研究了萃取劑用量、磁性材料用量、pH值、吸附時(shí)間、洗脫液組分、洗脫時(shí)間和洗脫次數(shù)等因素對(duì)TCs吸附效果的影響,結(jié)果表明:以NaCl為鹽析劑,MgSO4·7H2O為絡(luò)合劑,乙腈為萃取劑,利用分散固相萃取可將TCs從水相萃取至乙腈溶液中;以Fe_3O_4@SiO_2@APTES作為吸附劑,1m L萃取液加入90μL濃度為1mol/L的NaOH,以20mg的Fe_3O_4@SiO_2@APTES吸附10min可實(shí)現(xiàn)TCs的高效吸附;水:乙腈:高氯酸比例為86:10:4(V:V:V)的混合溶液洗脫5min可獲得較好的洗脫效果,4種TCs的吸附率在77.36%-99.04%之間。(3)牛奶樣品中TCs測(cè)定:采用實(shí)驗(yàn)建立的方法對(duì)牛奶中四種TCs進(jìn)行測(cè)定,方法線性范圍為0.05-2.5mg/L,相對(duì)標(biāo)準(zhǔn)偏差在3.85-9.30%之間,檢出限40μg/L,加標(biāo)回收率在87.78-107.48%之間。相對(duì)于國(guó)標(biāo)固相萃取方法,本研究建立的磁分散固相萃取方法具有操作簡(jiǎn)便、快速等優(yōu)點(diǎn),可滿足牛奶樣品TCs日常檢測(cè)的需求。2.基于SBA-15新基質(zhì)的喹諾酮類抗生素MALDI-TOF MS高通量檢測(cè)新技術(shù)傳統(tǒng)基質(zhì)多為小分子有機(jī)酸,MALDI測(cè)定時(shí)在低分子量范圍內(nèi)(500Da)會(huì)產(chǎn)生很強(qiáng)的基質(zhì)背景干擾。針對(duì)以上問題,實(shí)驗(yàn)在傳統(tǒng)基質(zhì)CHCA基礎(chǔ)上,引入SBA-15大分子介孔材料,制得改性CHCA新基質(zhì)SBA-15@APTES@CHCA并應(yīng)用于喹諾酮類抗生素的檢測(cè),建立了基于MALDI-TOF MS新基質(zhì)的12種喹諾酮類抗生素(QNs)檢測(cè)新方法。利用傳統(tǒng)CHCA基質(zhì)和SBA-15反應(yīng)所得的SBA-15@APTES@CHCA基質(zhì)不僅保留了傳統(tǒng)基質(zhì)吸收和傳遞激光能量的性質(zhì),而且通過SBA-15大分子的引入可有效消除傳統(tǒng)基質(zhì)在低分子量測(cè)定時(shí)的基質(zhì)背景干擾。主要研究?jī)?nèi)容包括:(1)SBA-15@APTES@CHCA新基質(zhì)的合成:實(shí)驗(yàn)利用SBA-15表面的羥基基團(tuán),通過APTES水解反應(yīng)制備了表面氨基化SBA-15@APTES前體;利用EDC和NHS酰胺反應(yīng),將CHCA的羧基進(jìn)行活化后與SBA-15@APTES偶聯(lián),制備了SBA-15@APTES@CHCA新基質(zhì)。傅里葉紅外光譜,掃描電鏡鑒定偶聯(lián)成功。(2)SBA-15@APTES@CHCA使用條件優(yōu)化:實(shí)驗(yàn)對(duì)基質(zhì)溶劑種類、基質(zhì)濃度、樣品基質(zhì)混合比、點(diǎn)樣方法等條件做了優(yōu)化,結(jié)果表明:選用乙腈:0.1%TFA(1+1)為基質(zhì)溶劑,1mg/m L基質(zhì)懸浮液,基質(zhì)與樣品體積比為1:6時(shí),采用混合點(diǎn)樣法可獲得較好的MALDI-TOF-MS分析信號(hào)。(3)喹諾酮類抗生素MALDI-TOF MS檢測(cè)方法建立:利用制備的新基質(zhì),在優(yōu)化好的條件下對(duì)12種QNs用MALDI-TOF MS進(jìn)行檢測(cè),可獲得較好的分析信號(hào),分別是:達(dá)氟沙星m/z 358(M+H)+,恩諾沙星m/z 360(M+H)+,環(huán)丙沙星m/z 332(M+H)+,二氟沙星m/z 400(M+H)+和m/z 422(M+Na)+,依諾沙星m/z321(M+H)+,加替沙星m/z 376(M+H)+,氟羅沙星m/z 370(M+H)+,洛美沙星m/z352(M+H)+,司帕沙星m/z 393(M+H)+,諾氟沙星m/z 320(M+H)+,左氧氟沙星m/z 362(M+H)+,培氟沙星m/z 334(M+H)+,12種QNs的方法檢出限在0.5-1.0mg/L之間。3.石墨烯功能化磁性材料在喹諾酮類抗生素MALDI-TOF MS高通量檢測(cè)中的應(yīng)用本研究以氨基功能化磁性微球?yàn)榛A(chǔ),在其表面進(jìn)一步修飾氧化石墨烯,制備了石墨烯功能化磁性材料(GO-NH-Fe_3O_4),并應(yīng)用于喹諾酮類抗生素的分離富集。結(jié)合前期建立的MALDI-TOF MS檢測(cè)技術(shù),建立了基于石墨烯功能化磁性材料的喹諾酮類抗生素MALDI-TOF MS檢測(cè)新技術(shù),并應(yīng)用于環(huán)境水樣的檢測(cè)。內(nèi)容主要包括:(1)GO-NH-Fe_3O_4的制備:實(shí)驗(yàn)在利用Hummer’s改良法制備氧化石墨烯基礎(chǔ)上,將氨基化磁性微球與氧化石墨烯偶聯(lián),制得石墨烯功能化磁性材料GO-NH-Fe_3O_4。FT-IR和SEM結(jié)果證明石墨烯氧化成功,氨基磁性微球成功偶聯(lián)到了氧化石墨烯表面,且在水中具有較好的分散性。(2)GO-NH-Fe_3O_4對(duì)QNs吸附效果研究:實(shí)驗(yàn)對(duì)磁性材料種類、pH值、吸附反應(yīng)時(shí)間、GO-NH-Fe_3O_4用量、洗脫液中氨水濃度、洗脫時(shí)間、洗脫次數(shù)進(jìn)行了優(yōu)化,結(jié)果表明:在弱酸性、中性或弱堿性條件下,3mL的GO-NH-Fe_3O_4與適量樣品反應(yīng)30min,可將樣品中的喹諾酮類抗生素吸附到GO-NH-Fe_3O_4材料上,質(zhì)譜圖中12種目標(biāo)物特征峰均能明顯辨別,吸附后殘液中檢測(cè)不到目標(biāo)物;用15%的氨水甲醇溶液對(duì)吸附劑洗脫15min,可獲得較好的洗脫效果。(3)水樣中QNs檢測(cè):在優(yōu)化的條件下利用GO-NH-Fe_3O_4磁性功能材料,結(jié)合MALDI-TOF MS方法對(duì)自來水、海河水、井水等水樣中的12種QNs進(jìn)行檢測(cè),結(jié)果表明:結(jié)合GO-NH-Fe_3O_4的富集凈化,利用MALDI-TOF-MS測(cè)定12種QNs方法的檢出限可達(dá)10μg/L。實(shí)驗(yàn)建立的方法具有高通量、檢測(cè)速度快等特性,可應(yīng)用于環(huán)境水中多種QNs的快速高通量篩查需要。
[Abstract]:In recent years, magnetic microspheres function as a new solid phase extraction material to obtain more and more attention. The microspheres were modified or modified, which can meet the pollutants in the aspects of extraction, separation and purification and so on. This research use different functional magnetic materials of tetracyclines (tetracycline, oxytetracycline, chlortetracycline, doxycycline), quinolones (pefloxacin, norfloxacin, fleroxacin, levofloxacin, enoxacin, lomefloxacin, two levofloxacin, sparfloxacin, ciprofloxacin, enrofloxacin, danofloxacin, gatifloxacin) adsorption characteristics of antibiotics, the establishment of a new technology of antibiotics detection of magnetic chromatography mass spectrometry with dispersive solid phase extraction based on the related research for to further explore and improve the new technology of high sensitivity detection of antibiotics, are of great significance to broaden the application range of magnetic materials. The main research contents. Including: 1. based on the new technology of tetracycline antibiotics HPLC detection of amino functionalized magnetic microspheres on the basis of Fe_3O_4 magnetic core, amino modified magnetic functional materials were prepared. The adsorption properties of different materials on TCs were investigated. The amino functionalized magnetic microspheres (MNP-NH2) in the organic phase of tetracycline (TCs) adsorption the characteristics of high efficiency, the dispersive solid phase extraction technology and magnetic solid phase extraction technology, 4 kinds of TCs magnetic dispersion test technique of solid phase extraction HPLC was established and used to detect milk samples. Contents include: (1) functional magnetic materials prepared by modified in our laboratory based on amino magnetic microsphere SBA-15, molecular mesoporous material is introduced into the preparation of magnetic functional materials, and further optimize the dosage of APTES, different specific surface area and the amino content of magnetic materials Fe_3O_4@ SBA-15@APTES and Fe_3O_4 the preparation @SiO_2@APTES. Fourier transform infrared spectroscopy, elemental analysis results confirm the successful coupling of p-nitrobenzaldehyde colorimetric method of magnetic material surface amino quantitative results showed that through the APTES control in the process of synthesis of amount of magnetic functional materials were prepared with different amino content. (2) functional magnetic materials on adsorption effect of TCs: Fe_3O_4@SiO_2@APTES in acetonitrile solution the TCs shows good adsorption properties. Experimental study of the extraction agent, magnetic material dosage, pH value, adsorption time, eluent composition, influence factors, adsorption elution time and elution times on TCs results show that NaCl as the salting out agent, MgSO4 7H2O as complexing agent, acetonitrile the extractant, using dispersive solid phase extraction can be TCs from aqueous extraction to acetonitrile; using Fe_3O_4@SiO_2@APTES as adsorbent, 90 L concentration added 1m L extraction solution is 1mol/L NaOH, 20mg F High e_3O_4@SiO_2@APTES adsorption 10min can achieve TCs; water: acetonitrile: perchloric acid ratio of 86:10:4 (V:V:V) of the mixed solution of 5min can obtain better elution elution, the adsorption rate of TCs 4 in 77.36%-99.04%. (3) the determination of TCs in milk samples: using the method of experiment based on four kinds of milk the determination of TCs, the linear range of the method was 0.05-2.5mg/L, the relative standard deviation between 3.85-9.30%, the detection limit of 40 g/L, the recovery rate was 87.78-107.48%. Compared with the national standard of solid phase extraction method, this study established the magnetic dispersion solid phase extraction method is simple, fast, and can meet the needs of daily milk samples TCs test.2. MALDI-TOF MS quinolones high-throughput SBA-15 new matrix detection technology based on the traditional matrix for small molecule organic acid, MALDI determination in low molecular weight range (500Da) will produce Matrix background of strong interference. To solve the above problems, the experiment in traditional matrix CHCA based on the introduction of SBA-15 molecular mesoporous materials, prepared modified CHCA matrix SBA-15@APTES@CHCA and applied to the detection of quinolone antibiotics, established 12 quinolones MALDI-TOF MS new matrix (QNs) based on a new method for the detection of SBA-15@APTES@CHCA matrix. By using the traditional CHCA matrix and SBA-15 reaction proceeds not only retains the properties of traditional matrix absorption and transmission of laser energy, and by introducing SBA-15 molecules can effectively eliminate the interference of matrix background of traditional matrix in low molecular weight determination. The main research contents include: (1) a synthetic SBA-15@APTES@CHCA matrix: experiments with hydroxyl groups the surface of SBA-15, the surface amino SBA-15@APTES precursor prepared by APTES hydrolysis; using EDC and NHS amide reaction, the carboxyl groups were CHCA After the activation of SBA-15@APTES@CHCA and SBA-15@APTES coupling, a new matrix was prepared. Fourier transform infrared spectroscopy, scanning electron microscopy identification successfully coupled. (2) SBA-15@APTES@CHCA using the optimal conditions: experiment on matrix solvent, substrate concentration, mixing ratio of the sample matrix, condition sampling method for optimization, the results show that the acetonitrile (1+1): 0.1%TFA as the matrix solvent, 1mg/m matrix and L matrix suspension, sample volume ratio was 1:6, the mixed sample method can obtain better MALDI-TOF-MS signal analysis. (3) MALDI-TOF MS quinolone antibiotics detection method established: using the new matrix preparation, the optimized conditions of 12 kinds of QNs MALDI-TOF MS for testing, can obtain better signal analysis, respectively is: m/z 358 + danofloxacin (M+H), enrofloxacin (M+H) m/z 360 +, m/z 332 + ciprofloxacin (M+H), two m/z (M+H) loxacin 400 + and m/z 422 + (M+Na), enoxacine M /z321 (M+H) + m/z (M+H), gatifloxacin 376 +, m/z 370 + (M+H) of fleroxacin, lomefloxacin (m/z352 M+H) + m/z (M+H), sparfloxacin 393 +, m/z 320 + norfloxacin (M+H), levofloxacin (M+H) m/z 362 +, pefloxacin (M+H) + m/z 334 12 kinds of methods, the detection limit of QNs between 0.5-1.0mg/L application of.3. functionalized graphene magnetic materials in MALDI-TOF MS high-throughput detection of quinolone antibiotics in this study on amino functionalized magnetic microspheres based on the surface modification of graphene oxide to graphene, functional magnetic materials were prepared (GO-NH-Fe_3O_4), and separation applied to quinolones enrichment. Combined with MALDI-TOF MS detection technology pre established, established a new technique for the detection of quinolone antibiotics MALDI-TOF MS functionalized graphene based magnetic materials, and apply in the detection of environmental samples. The main contents include: (1) GO-NH-Fe_3O_4 Preparation: the experiment in the use of Hummer s prepared by a modified method of graphene oxide based on the coupling of magnetic microspheres and amino functionalized graphene oxide, prepared graphene functional magnetic materials GO-NH-Fe_3O_4.FT-IR and SEM results show that graphene oxide, amino magnetic microspheres successfully coupled to the graphene oxide surface, and has good dispersion in the water. (2) study on the effect of adsorption of GO-NH-Fe_3O_4 on QNs: the experiment of magnetic materials, pH value, adsorption time, dosage of GO-NH-Fe_3O_4, the elution time of elution solution, ammonia concentration, were optimized. The results showed that: in the times of elution of weakly acidic, neutral or alkaline conditions, the amount of GO-NH-Fe_3O_4 and 3mL sample reaction 30min, can be in a sample of quinolones adsorbed to the GO-NH-Fe_3O_4 material, the mass spectrum of 12 target peaks can significantly distinguish, after adsorption residue was not detected in. Standard; 15min elution adsorbent with ammonia of 15% methanol solution, elution can obtain better effect. (3) QNs in water detection: using GO-NH-Fe_3O_4 magnetic functional materials under the optimized conditions, combined with the MALDI-TOF MS method of tap water, sea water, 12 QNs wells in water samples were detected, results show that according to GO-NH-Fe_3O_4 enrichment and purification, detection limit of up to 10 g/L. to establish experimental determination of 12 QNs by MALDI-TOF-MS method with high throughput, fast detection speed and other characteristics, rapid high-throughput screening can be applied to a variety of environmental water QNs.

【學(xué)位授予單位】：中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：TQ465;O657.63

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