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服用Suldox后血清和尿液中乙胺嘧啶、周效磺胺及其N4-乙酰代谢物的高效液相色谱测定法

High-performance liquid chromatographic assay of pyrimethamine, sulfadoxine and its N4-acetyl metabolite in serum and urine after ingestion of Suldox.

作者信息

Midskov C

出版信息

J Chromatogr. 1984 Jun 8;308:217-27. doi: 10.1016/s0021-9673(01)87548-8.

DOI:10.1016/s0021-9673(01)87548-8
PMID:6378948
Abstract

A sensitive and selective reversed-phase high-performance liquid chromatographic assay has been developed to determine the concentration of pyrimethamine, sulfadoxine and N4-acetylsulfadoxine in serum and urine after oral administration of the antimalarial remedy Suldox. Hitherto the literature describes no method being able to quantitate all three compounds in these fluids. The compounds are extracted successively from the same sample and subjected to liquid chromatography followed by ultraviolet detection (280 nm). Calibration curves were linear (r2 = 0.999; S.E.M. less than 3%; n = 10) in the range 0-300 micrograms/ml (sulfadoxine) and 0-1000 ng/ml (N4-acetylsulfadoxine and pyrimethamine). The limits of quantitation for the latter compounds were as low as about 5 ng/ml and 1 ng/ml, respectively. At therapeutic serum concentrations of 30 micrograms/ml (sulfadoxine), 350 ng/ml (N4-acetylsulfadoxine) and 120 ng/ml (pyrimethamine) an interassay reproducibility below 8% (relative standard deviation) was found for all three compounds. The assay was evaluated in a pilot study and proved convenient for pharmacokinetic studies in man following oral co-administration of pyrimethamine and sulfadoxine.

摘要

已开发出一种灵敏且具选择性的反相高效液相色谱分析法,用于测定口服抗疟药物Suldox后血清和尿液中乙胺嘧啶、磺胺多辛及N4 - 乙酰磺胺多辛的浓度。迄今文献中尚无能够对这些体液中的这三种化合物进行定量分析的方法。这些化合物从同一样品中依次萃取,然后进行液相色谱分析,接着采用紫外检测(280 nm)。校准曲线在0 - 300微克/毫升(磺胺多辛)和0 - 1000纳克/毫升(N4 - 乙酰磺胺多辛和乙胺嘧啶)范围内呈线性(r2 = 0.999;标准误小于3%;n = 10)。后两种化合物的定量限分别低至约5纳克/毫升和1纳克/毫升。在治疗性血清浓度为30微克/毫升(磺胺多辛)、350纳克/毫升(N4 - 乙酰磺胺多辛)和120纳克/毫升(乙胺嘧啶)时,发现这三种化合物的批间重现性均低于8%(相对标准偏差)。该分析方法在一项初步研究中进行了评估,结果证明对于口服乙胺嘧啶和磺胺多辛后人体的药代动力学研究很方便。

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