摘要
原子吸收光谱法是一种传统的分析方法，由于其灵敏、简便、快速、准确和选择性高，使其在金属元素分析中得到了广泛应用和发展。但其不能直接应用于有机化合物的测定，这就限制了原子吸收光谱法的应用范围。本文研究建立了流动注射-在线固相萃取-原子吸收光谱法测定盐酸左氧氟沙星、加替沙星等药物的分析方法，探讨了分析测定条件，并应用于药物制剂等样品的测定，获得满意的结果。
本研究论文内容包括综述和研究报告两部分内容。
第一部分：综述
对近年来所发表的有关间接原子吸收光谱法在药物分析中的应用及进展作了详细的综述。内容包括：间接原子吸收光谱法的方法原理及其应用，流动注射-间接原子吸收光谱法在药物分析中的应用与发展，原子吸收联用技术的发展展望。
第二部分：研究报告
1流动注射-在线固相萃取-间接原子吸收光谱法测定药物中盐酸左氧氟沙星的含量
本文建立了一种简单快速的检测药物制剂中盐酸左氧氟沙星含量的流动注射-在线固相萃取-火焰原子吸收间接测定法。该方法是基于左氧氟沙星与Fe(Ⅲ)在线定量连续生成阳离子络合物后，再与离子对试剂NH_4ClO_4中ClO_4~-结合形成中性离子对缔合物，由于C_(18)对反应生成的离子对缔合物有吸附，而对剩余未反应的Fe(Ⅲ)无吸附，因此可将二者分离，然后用乙醇溶液(60％)洗脱吸附的离子对缔合物，以FAAS法测定洗脱液中离子对缔合物中Fe(Ⅲ)的含量来间接测定左氧氟沙星的含量。当吸附时间为60s，采样速率为8.0mL·min~(-1)时，左氧氟沙星浓度在0.2-10.0μg·mL~(-1)范围内与原子吸收的吸光度值呈良好的线性关系，相关系数为0.9980，检出限为0.08μg·mL~(-1)，相对标准偏差(RSD)为1.6％(c=5.0μg·mL~(-1)左氧氟沙星，n=11)。该方法应用于药物制剂中盐酸左氧氟沙星的含量测定，结果令人满意。
2流动注射-在线离子对固相萃取-间接原子吸收光谱法测定药物中加替沙星的含量
提出了一个流动注射在线离子对固相萃取火焰原子吸收光谱法间接分析加替沙星的测定体系。在这个体系中，加替沙星在适当的酸度条件下与Fe(Ⅲ)形成2：1的阳离子络合物，再与离子对试剂ClO_4~-结合形成中性离子对缔合物，通过C_(18)固相萃取柱吸附反应生成的离子对缔合物，剩余未反应的Fe(Ⅲ)用水清洗后，再用乙醇、水和乙腈的混合液(48：32：20)洗脱吸附在C_(18)固相萃取柱上的离子对缔合物送至原子吸收检测器中加以测定。在最优化条件下，当反应萃取时间为60s时，加替沙星浓度在0.05-12.50μg·mL~(-1)范围内与原子吸收的吸光度呈良好的线性关系，检出限为0.02μg·mL~(-1)，采样频率为24次／小时，对5.0μg·mL~(-1)的加替沙星进行11次测定，其相对标准偏差(RSD)为2.0％。该方法用于胶囊和片剂中加替沙星含量的测定，其结果与紫外分光光度法结果一致，回收率为95％-106％。
The atomic absorption spectrometry is a traditional analytical method.Flame atomic absorption spectrometry (FAAS), which is frequently used for thedetermination of metal ions because of relatively high sensitivity and selectivity, is lessused for indirect determination of organic species. This thesis has studied the analyticalmethod of determination of levofloxacin, gatifloxacin by flow injection on-line solidphase extraction flame atomic absorption spectrometry. The method has been applied tothe analysis of pharmaceutical samples with satisfactory results.
There are two parts in this thesis: review and study reports.
Part One: review
The application and progress of indirect flame atomic absorption spectrometry(FAAS) is reviewed, including analysis principle, application of indirect AAS inpharmaceutical analysis, application and development of FIA-AAS indirect method andprogress of AAS coupling technique.
Part Two: study reports
1. Flow Injection On-line Solid Phase Extraction Flame Atomic AbsorptionSpectrometry for Indirect Analysis of Levofloxacin.
A novel approach for the indirect analysis of levofloxacin was developed withflame atomic absorption spectrometry (FAAS) coupled to flow injection (FI) on-linesolid-phase extraction (SPE). The method is based on the adsorbing preconcentrationand separation of levofloxacin as an ion-pair complex of levofloxacin-Fe(Ⅲ)-ClO_4 on aC_(18) extraction column and FAAS detection of Fe(Ⅲ) in the ion-pair complex elutedsubsequently with ethanol. The effects of various experimental conditions wereinvestigated. At a 60 s adsorption time and 8.0 mL.min~(-1) sample consumption rate, thecalibration curve was linear over the range of 0.2-10.0μg.mL~(-1) with with a linear correlation of 0.9980. The detection limit was 0.08μg·mL~(-1). The precision (%RSD) for11 replicate measurements of 5.0μg·mL~(-1) levofloxacin was 1.6%. The proposedmethod was applied to the analysis of levofloxacin in pharmaceutical formulations withsatisfactory results.
2. On-line ion-pair solid phase extraction flow injection flame atomic absorptionspectrometry for indirect determination of gatifloxacin.
A flow injection flame atomic absorption spectrometry (FAAS) with on-lineion-pair solid phase extraction (IP SPE) was developed for indirect determination ofgatifloxacin. In a flow injection system, gatifloxacin reacted first with ferric to form a2:1 complex cation, then the cation reacted with ClO_4~- to form a neutral ion-paircomplex of gatifloxacin-Fe (Ⅲ)-ClO_4 and adsorbed on C_(18) solid phase extractioncolumn, while excessive ferric was washed with H_2O to waste. The ion-pair complexadsorbed was eluted with the mixture of ethanol, water and acetonitrile (48:32:20, v/v/v)and Fe (Ⅲ) in the complex was determined with FAAS. The optimization of variousexperimental conditions was investigated. When the reaction and extraction time was 60s, the calibration curve was linear in the range from 0.05 to12.50μg.mL~(-1) with a relativestandard deviations of 2.0% (n=11, c=5.0μg·mL~(-1)), and the detection limit was 0.02μg.mL~(-1) of gatifloxacin. The analytical frequency was 24 per hour. The method wasvalidated by analysis of gatifloxacin in capsules and tablets, and the results agreed wellwith those obtained by the UV method. The recoveries obtained were 95%-106%.
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