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电化学评价和测定抗逆转录病毒药物福沙那韦使用掺硼金刚石和玻碳电极。

Electrochemical evaluation and determination of antiretroviral drug fosamprenavir using boron-doped diamond and glassy carbon electrodes.

机构信息

Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara, 06100, Turkey.

Faculty of Art & Science, Department of Chemistry, Hitit University, Corum, 19040, Turkey.

出版信息

Anal Bioanal Chem. 2010 May;397(1):189-203. doi: 10.1007/s00216-009-3334-3. Epub 2009 Dec 10.

Abstract

Fosamprenavir is a pro-drug of the antiretroviral protease inhibitor amprenavir and is oxidizable at solid electrodes. The anodic oxidation behavior of fosamprenavir was investigated using cyclic and linear sweep voltammetry at boron-doped diamond and glassy carbon electrodes. In cyclic voltammetry, depending on pH values, fosamprenavir showed one sharp irreversible oxidation peak or wave depending on the working electrode. The mechanism of the oxidation process was discussed. The voltammetric study of some model compounds allowed elucidation of the possible oxidation mechanism of fosamprenavir. The aim of this study was to determine fosamprenavir levels in pharmaceutical formulations and biological samples by means of electrochemical methods. Using the sharp oxidation response, two voltammetric methods were described for the determination of fosamprenavir by differential pulse and square-wave voltammetry at the boron-doped diamond and glassy carbon electrodes. These two voltammetric techniques are 0.1 M H(2)SO(4) and phosphate buffer at pH 2.0 which allow quantitation over a 4 x 10(-6) to 8 x 10(-5) M range using boron-doped diamond and a 1 x 10(-5) to 1 x 10(-4) M range using glassy carbon electrodes, respectively, in supporting electrolyte. All necessary validation parameters were investigated and calculated. These methods were successfully applied for the analysis of fosamprenavir pharmaceutical dosage forms, human serum and urine samples. The standard addition method was used in biological media using boron-doped diamond electrode. No electroactive interferences from the tablet excipients or endogenous substances from biological material were found. The results were statistically compared with those obtained through an established HPLC-UV technique; no significant differences were found between the voltammetric and HPLC methods.

摘要

福沙那韦是一种抗逆转录病毒蛋白酶抑制剂安普那韦的前体药物,可在固体电极上被氧化。本研究采用循环伏安法和线性扫描伏安法,在掺硼金刚石电极和玻碳电极上研究了福沙那韦的阳极氧化行为。在循环伏安法中,根据 pH 值的不同,福沙那韦在两种工作电极上均显示出一个尖锐的不可逆氧化峰或波。本文讨论了氧化过程的机制。对一些模型化合物的伏安研究有助于阐明福沙那韦的可能氧化机制。本研究旨在通过电化学方法测定药物制剂和生物样品中的福沙那韦水平。利用尖锐的氧化响应,在掺硼金刚石和玻碳电极上,通过差分脉冲伏安法和方波伏安法描述了两种测定福沙那韦的伏安法。这两种伏安技术均采用 0.1 M H(2)SO(4)和 pH 2.0 的磷酸盐缓冲液,在掺硼金刚石电极上的定量范围为 4 x 10(-6)至 8 x 10(-5) M,在玻碳电极上的定量范围为 1 x 10(-5)至 1 x 10(-4) M,分别在支持电解质中。研究并计算了所有必要的验证参数。这些方法成功地应用于福沙那韦药物制剂、人血清和尿液样品的分析。在生物介质中,使用掺硼金刚石电极采用标准加入法。未发现来自片剂赋形剂或生物材料内源性物质的电活性干扰。将结果与通过建立的 HPLC-UV 技术获得的结果进行了统计学比较;未发现伏安法和 HPLC 法之间有显著差异。

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