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纳曲酮在商业制剂和人体液中的伏安法:定量和药代动力学研究。

Voltammetry of naltrexone in commercial formulation and human body fluids: Quantification and pharmacokinetic studies.

机构信息

Analytical and Electrochemistry Research Unit, Chemistry Department, Faculty of Science, Tanta University, 31527 Tanta, Egypt.

出版信息

Bioelectrochemistry. 2011 Jun;81(2):65-73. doi: 10.1016/j.bioelechem.2011.02.005. Epub 2011 Feb 21.

Abstract

Naltrexone HCl (NAL.HCl) has been reduced at the mercury electrode in Britton-Robinson universal buffer of pH values 2-11 with a mechanism involving the quasi-reversible uptake of the first transferring electron followed by a rate-determining protonation step of its C=O double bond at position C-6. Simple, sensitive, selective and reliable linear-sweep and square-wave adsorptive cathodic stripping voltammetry methods have been described for trace quantitation of NAL.HCl in bulk form, commercial formulation and human body fluids without the necessity for sample pretreatment and/or time-consuming extraction steps prior to the analysis. Limits of quantitation of 6.0×10(-9)M and 8.0×10(-10)M NAL.HCl in bulk form or commercial formulation and of 9.0×10(-9) and 1.0×10(-9)M NAL.HCl in spiked human serum samples were achieved by the described linear and square-wave stripping voltammetry methods, respectively. Furthermore, pharmacokinetic parameters of the drug in human plasma samples of healthy volunteers following the administration of an oral single dose of 50mg NAL.HCl (one Revia(®) tablet) were estimated by means of the described square-wave stripping voltammetry method without interferences from the drug's metabolites and/or endogenous human plasma constituents. The estimated pharmacokinetic parameters were favorably compared with those reported in literature.

摘要

盐酸纳曲酮(NAL.HCl)在 pH 值为 2-11 的 Britton-Robinson 通用缓冲液中于汞电极上被还原,其机制涉及第一个转移电子的准可逆摄取,随后是其 C=O 双键在 C-6 位置的速率决定质子化步骤。已经描述了简单、灵敏、选择性和可靠的线性扫描和方波吸附阴极溶出伏安法,用于痕量定量分析 NAL.HCl 的块状形式、商业制剂和人体体液,而无需在分析前进行样品预处理和/或耗时的提取步骤。通过所描述的线性和方波溶出伏安法,在块状形式或商业制剂中的 NAL.HCl 的定量下限分别为 6.0×10(-9)M 和 8.0×10(-10)M,在加标人血清样品中的 NAL.HCl 的定量下限分别为 9.0×10(-9)和 1.0×10(-9)M。此外,通过所描述的方波溶出伏安法,在健康志愿者口服单剂量 50mg NAL.HCl(一片 Revia(®) 片)后,在人血浆样品中估算了该药物的药代动力学参数,没有来自药物代谢物和/或内源性人血浆成分的干扰。所估计的药代动力学参数与文献中报道的参数相符。

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