牛奶中β-内酰胺类抗生素检测方法的研究
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摘要
β-内酰胺类抗生素是指分子结构中含有β-内酰胺环的抗生素,因其良好的抗菌作用,目前在牲畜疾病治疗和预防中应用最多的抗生素之一。然而不规范用药会引起畜禽产品尤其是动物乳汁中的药物残留,对人体健康不利。因此,建立一类高效、准确、简便的β-内酰胺类抗生素检测方法就显得尤为重要。本文主要研究了β-内酰胺类抗生素中常见的几种药物如青霉素G、氨苄西林、头孢噻呋钠、头孢拉定的分析检测新方法,主要的研究内容如下：
第一部分：研究了青霉素G存在下双氧水氧化苋菜红的褪色反应,分别在两段浓度范围内建立了催化动力学光度法测定微量青霉素G的方法。具体为低浓度范围内青霉素G催化动力学光度法,方法线性范围为0.20～4.00μg/mL,回归方程y=-0.015x+ 0.311(x:μg/mL),r=0.9998；较高浓度范围内青霉素G阻抑动力学光度法,方法线性范围为4.00～50.0μg/mL,回归方程y=0.001x+0.280(x:μg/mL),r=0.9997。并对反应机理进行了探讨。方法的测定波长均为520nm,检出限为1.0×10-7g/mL,最大相对标准偏差为1.23%,回收率为96.7%～104.1%。
第二部分：建立了表面活性剂增敏动力学光度法测定牛奶中氨苄西林药物残留的方法。利用中性介质中阳离子表面活性剂Triton100对氨苄西林催化二甲酚橙褪色反应的增敏作用,在pH=7.0的Tris-HCL缓冲溶液中,测定牛奶样品中的氨苄西林药物残留,线性范围为0.10～50.00μg/mL,回归方程为y=0.240x+2.151,r=0.9972,检出限为2.0×10-8g/mL,最大相对标准偏差为1.15%,回收率为98.1%～103.6%。本法用于实际样品检测获得满意结果。此方法简便、快捷、准确,可用于大量牛奶样品中氨苄西林的快速初筛及检测。
第三部分：在pH=7.00的Britton-Robinson(B-R)缓冲溶液及表面活性剂高级脂肪醇聚氧乙烯醚硫酸钠(AES)介质中,吖啶橙-中性红能够发生有效的能量转移,使中性红荧光增强。头孢噻呋钠的加入又使得中性红的荧光猝灭,据此建立了测定头孢噻呋钠的新方法。将此方法用于牛奶中头孢噻呋钠药物残留的测定,方法线性范围为0.10～60.00μg/mL,回归方程为y=399.7x+38.88,r=0.9980,检出限为0.1×10-7g/mL,最大相对标准偏差为1.19%,回收率为95.9%～102.7%。本法用于实际样品检测并与高效液相色谱法进行对比,结果满意。实验表明,该方法简单、快速、灵敏、准确。
第四部分：根据头孢类药物对牛血清白蛋白的荧光具有猝灭的特性,建立了一种测定牛奶中两种头孢类药物的新方法。检测体系的最大激发波长为280m,最大发射波长为341nm。头孢噻呋钠含量(x)为0.10～30.00μg/mL时,ΔF与头孢噻呋钠的含量呈线性关系,回归方程为y=563.1x+360.5,r=0.9998,头孢噻呋钠的检出限为0.5×10-7g/mL。头孢拉定含量(x)为2.50～80.0μg/mL时,ΔF与头孢拉定的含量呈线性关系,回归方程y=312x+90.1(x:μg/mL),r=0.9999.该法测定头孢拉定的检出限为1.0×10-7g/mL。实验表明,该方法简单、快速、灵敏、准确。
The unique structure of (3-lactam antibiotics is theβ-lactam ring, it is one of the most widespread antibiotics. Antibioties are widely used for animal clinic therapy, and are frequently added into feeds of the prevention or treatments of animal diseases. However, illegal administration will lead to residues in edible tissues, especially in the milk of galaetophorous animals, and finally do latent harm to human health. Thus, it is significant to develop a series of sensitive, reliable and convenient methods for the determination of penicillin antibiotics. In this paper, fluorescence analysis of common ofβ-lactam class-antibiotic, such as penicillin G, ampicillin, ceftiofur sodium and cefradine have been studied. The main contents are as follows:
Part 1:Catalytic kinetic spectrophotometric determination of penicillin G and mechanism analysis
The new catalytic kinetic spectrophotometry with amaranth fading for determining trace amounts of penicillin G was proposed using hydrogen peroxide as oxidizing agent. The low concentration range of penicillin G obeys catalytic kinetic spectrophotometric mechanism analysis, the linear range of determination was 0.20～4.00μg/mL, the regression equation is y=-0.015x+0.311(x:μg/mL),r=0.9998. And the higher concentration range obeys inhibitory kinetics spectrophotometric mechanism analysis, the linear range of determination was 4.00～50.0μg/mL, and y=0.001x +0.280(x:ug/mL), r=0.9997. The wavelength for determination is 520nm. The detection limit is 1.0×10-7g/mL. The maximum relative standard deviation is 1.23%. The recovery is 96.7%～104.1%.
Part 2:Kinetic spectrophotometric determination of trace ampicillin in milk with sensitization effect of surfactant
A catalytic kinetic spectrophotometric method for the determination ampicillin in milk has been developed. It was based on the catalytic effect of ampicillin on the reaction between xylenol orange and aquae hydrogenii dioxide with Tris-HCl buffer solution (pH=7.0)and Triton100. Experimental conditions, such as reaction time, temperature, and the concentration of reagents were optimized by measuring the absorbance at 580nm.Under the best condition, the detection limit was 2.0×10-8g/mL with linear range of 0.10～ 50.00μg/mL. The linear equation was y=0.240x+2.151, r=0.9972. The recovery was between 98.1%and 103.6%. This method is quick, stable and with little interferences. It has been applied for the detection of ampicillin in milk.
Part 3:Fluorescence resonance energy transfer quenching for determina-tion of trace ceftiofur sodium in milk
It was found that the effective energy transfer could occur between acridine orange and neutral red in the surfactant AES solution containing Britton-Robinson solution(pH=7.00), which improved the fluorescence intensity of neutral red. The fluorescence of acridine orange-neutral red systems was quenched with the addition of ceftiofur sodium. Therefore, a novel fluorescence quenching method was developed for indirect determination of ceftiofur sodium by acridine orange-neutral red fluorescence resonance energy transfer. This method has been applied for the determination of ceftiofur sodium in milk, and the analytical results were in agreement with those obtained by the HPLC method. The detection limit was 0.1 X 10-7g/mL with linear range of 0.10μ～60.00μg/mL. The linear equation was y= 399.7x+38.88, r=0.9980. The recovery was between 95.9%～102.7%. This method is quick, stable and with little interferences. It has been applied for the detection of ampicillin in milk.
Part 4:Determination of cephalosporins B antibiotics in milk based on the fluorescence quenching of bovine serum albumin
A new method for the determination of trace amounts of cephalosporins B antibiotics has been developed. This method is based on the quenching of fluorescence of bovine serum albumin(BSA). The excitation and emission wavelengths were found to be 280 nm and 341 nm, respectively. The detection limit was 0.5×10-7g/mL with linear range of 0.10～30.00μg/mL for the ceftiofur sodium determination, and its linear equation was y= 563.lx+360.5 (x:μg/mL), r=0.9998, its recovery was between 90.2%～98.5%. The detection limit was 1.0×10-7g/mL with linear range of 2.50～80.0μg/mL for the cefradine determination, and its linear equation was y=312x+90.1 (x:μg/mL), r=0.9999, its recovery was between 90.1%～97.4%.This method is quick, stable and with little interferences. It has been applied for the detection of ceftiofur sodium and cefradine in milk.
第一部分：研究了青霉素G存在下双氧水氧化苋菜红的褪色反应,分别在两段浓度范围内建立了催化动力学光度法测定微量青霉素G的方法。具体为低浓度范围内青霉素G催化动力学光度法,方法线性范围为0.20～4.00μg/mL,回归方程y=-0.015x+ 0.311(x:μg/mL),r=0.9998；较高浓度范围内青霉素G阻抑动力学光度法,方法线性范围为4.00～50.0μg/mL,回归方程y=0.001x+0.280(x:μg/mL),r=0.9997。并对反应机理进行了探讨。方法的测定波长均为520nm,检出限为1.0×10-7g/mL,最大相对标准偏差为1.23%,回收率为96.7%～104.1%。
第二部分：建立了表面活性剂增敏动力学光度法测定牛奶中氨苄西林药物残留的方法。利用中性介质中阳离子表面活性剂Triton100对氨苄西林催化二甲酚橙褪色反应的增敏作用,在pH=7.0的Tris-HCL缓冲溶液中,测定牛奶样品中的氨苄西林药物残留,线性范围为0.10～50.00μg/mL,回归方程为y=0.240x+2.151,r=0.9972,检出限为2.0×10-8g/mL,最大相对标准偏差为1.15%,回收率为98.1%～103.6%。本法用于实际样品检测获得满意结果。此方法简便、快捷、准确,可用于大量牛奶样品中氨苄西林的快速初筛及检测。
第三部分：在pH=7.00的Britton-Robinson(B-R)缓冲溶液及表面活性剂高级脂肪醇聚氧乙烯醚硫酸钠(AES)介质中,吖啶橙-中性红能够发生有效的能量转移,使中性红荧光增强。头孢噻呋钠的加入又使得中性红的荧光猝灭,据此建立了测定头孢噻呋钠的新方法。将此方法用于牛奶中头孢噻呋钠药物残留的测定,方法线性范围为0.10～60.00μg/mL,回归方程为y=399.7x+38.88,r=0.9980,检出限为0.1×10-7g/mL,最大相对标准偏差为1.19%,回收率为95.9%～102.7%。本法用于实际样品检测并与高效液相色谱法进行对比,结果满意。实验表明,该方法简单、快速、灵敏、准确。
第四部分：根据头孢类药物对牛血清白蛋白的荧光具有猝灭的特性,建立了一种测定牛奶中两种头孢类药物的新方法。检测体系的最大激发波长为280m,最大发射波长为341nm。头孢噻呋钠含量(x)为0.10～30.00μg/mL时,ΔF与头孢噻呋钠的含量呈线性关系,回归方程为y=563.1x+360.5,r=0.9998,头孢噻呋钠的检出限为0.5×10-7g/mL。头孢拉定含量(x)为2.50～80.0μg/mL时,ΔF与头孢拉定的含量呈线性关系,回归方程y=312x+90.1(x:μg/mL),r=0.9999.该法测定头孢拉定的检出限为1.0×10-7g/mL。实验表明,该方法简单、快速、灵敏、准确。
The unique structure of (3-lactam antibiotics is theβ-lactam ring, it is one of the most widespread antibiotics. Antibioties are widely used for animal clinic therapy, and are frequently added into feeds of the prevention or treatments of animal diseases. However, illegal administration will lead to residues in edible tissues, especially in the milk of galaetophorous animals, and finally do latent harm to human health. Thus, it is significant to develop a series of sensitive, reliable and convenient methods for the determination of penicillin antibiotics. In this paper, fluorescence analysis of common ofβ-lactam class-antibiotic, such as penicillin G, ampicillin, ceftiofur sodium and cefradine have been studied. The main contents are as follows:
Part 1:Catalytic kinetic spectrophotometric determination of penicillin G and mechanism analysis
The new catalytic kinetic spectrophotometry with amaranth fading for determining trace amounts of penicillin G was proposed using hydrogen peroxide as oxidizing agent. The low concentration range of penicillin G obeys catalytic kinetic spectrophotometric mechanism analysis, the linear range of determination was 0.20～4.00μg/mL, the regression equation is y=-0.015x+0.311(x:μg/mL),r=0.9998. And the higher concentration range obeys inhibitory kinetics spectrophotometric mechanism analysis, the linear range of determination was 4.00～50.0μg/mL, and y=0.001x +0.280(x:ug/mL), r=0.9997. The wavelength for determination is 520nm. The detection limit is 1.0×10-7g/mL. The maximum relative standard deviation is 1.23%. The recovery is 96.7%～104.1%.
Part 2:Kinetic spectrophotometric determination of trace ampicillin in milk with sensitization effect of surfactant
A catalytic kinetic spectrophotometric method for the determination ampicillin in milk has been developed. It was based on the catalytic effect of ampicillin on the reaction between xylenol orange and aquae hydrogenii dioxide with Tris-HCl buffer solution (pH=7.0)and Triton100. Experimental conditions, such as reaction time, temperature, and the concentration of reagents were optimized by measuring the absorbance at 580nm.Under the best condition, the detection limit was 2.0×10-8g/mL with linear range of 0.10～ 50.00μg/mL. The linear equation was y=0.240x+2.151, r=0.9972. The recovery was between 98.1%and 103.6%. This method is quick, stable and with little interferences. It has been applied for the detection of ampicillin in milk.
Part 3:Fluorescence resonance energy transfer quenching for determina-tion of trace ceftiofur sodium in milk
It was found that the effective energy transfer could occur between acridine orange and neutral red in the surfactant AES solution containing Britton-Robinson solution(pH=7.00), which improved the fluorescence intensity of neutral red. The fluorescence of acridine orange-neutral red systems was quenched with the addition of ceftiofur sodium. Therefore, a novel fluorescence quenching method was developed for indirect determination of ceftiofur sodium by acridine orange-neutral red fluorescence resonance energy transfer. This method has been applied for the determination of ceftiofur sodium in milk, and the analytical results were in agreement with those obtained by the HPLC method. The detection limit was 0.1 X 10-7g/mL with linear range of 0.10μ～60.00μg/mL. The linear equation was y= 399.7x+38.88, r=0.9980. The recovery was between 95.9%～102.7%. This method is quick, stable and with little interferences. It has been applied for the detection of ampicillin in milk.
Part 4:Determination of cephalosporins B antibiotics in milk based on the fluorescence quenching of bovine serum albumin
A new method for the determination of trace amounts of cephalosporins B antibiotics has been developed. This method is based on the quenching of fluorescence of bovine serum albumin(BSA). The excitation and emission wavelengths were found to be 280 nm and 341 nm, respectively. The detection limit was 0.5×10-7g/mL with linear range of 0.10～30.00μg/mL for the ceftiofur sodium determination, and its linear equation was y= 563.lx+360.5 (x:μg/mL), r=0.9998, its recovery was between 90.2%～98.5%. The detection limit was 1.0×10-7g/mL with linear range of 2.50～80.0μg/mL for the cefradine determination, and its linear equation was y=312x+90.1 (x:μg/mL), r=0.9999, its recovery was between 90.1%～97.4%.This method is quick, stable and with little interferences. It has been applied for the detection of ceftiofur sodium and cefradine in milk.
引文
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