Cañada-Cañada Florentina, Espinosa-Mansilla Anunciación, Muñoz de la Peña Arsenio, Mancha de Llanos Alicia
Department of Analytical Chemistry, University of Extremadura, 06071 Badajoz, Spain.
Anal Chim Acta. 2009 Aug 19;648(1):113-22. doi: 10.1016/j.aca.2009.06.045. Epub 2009 Jun 24.
A liquid chromatographic method for the simultaneous analysis of marker pteridins and biopterin reduced forms, in urine samples is proposed. A Zorbax Eclipse XDB-C18 column was used for the chromatographic separation, using a 98/2 (v/v), citrate buffer (pH 5.5)-acetonitrile mobile phase, in isocratic mode. A post-column photoderivatization was carried out with an on-line photoreactor, located between a diode array detector (DAD) and a fast scanning fluorescence detector (FSFD). Neopterin (NEO), biopterin (BIO), pterin (PT) and dihydrobiopterin (BH2) were determined by measuring native fluorescence, using the photoreactor in OFF-mode, and tetrahydrobiopterin (BH4) was determined by measuring of the induced fluorescence of the generated photoproducts, using the photoreactor in ON-mode. In addition, Creatinine (CREA), as a reference of metabolites excrection in urine, was simultaneously determined using the DAD detector. Detection limits were 0.2, 13.0, 0.3, 0.3 and 3.5 ng mL(-1), for NEO, BH2, BIO, PT and BH4, respectively, and 0.4 microg mL(-1) for CREA. Ratio values for NEO/CREA, PT/CREA, BH4/CREA, BH2/CREA, NEO/BIO and BIO(total)/CREA, in urine samples, of healthy children and adults, phenylketonuric children and infected mononucleosis children, are reported. A comparative study, about the mean values obtained for each of the compounds, by the present procedure and by the classical iodine oxidation method (Fukushimas method), has been performed, in urine samples belonging to healthy volunteers. The values obtained were BH4/CREA: 0.41, BH2/CREA: 0.31 and BIO(total)/CREA: 0.73, by the proposed method, and BH4/CREA: 0.35, BH2/CREA: 0.20 and BIO(total)/CREA: 0.48, by iodine oxidation method.
本文提出了一种用于同时分析尿液样本中标记蝶呤和生物蝶呤还原形式的液相色谱方法。采用Zorbax Eclipse XDB-C18色谱柱进行色谱分离,流动相为98/2(v/v)的柠檬酸盐缓冲液(pH 5.5)-乙腈,采用等度洗脱模式。在二极管阵列检测器(DAD)和快速扫描荧光检测器(FSFD)之间的在线光反应器上进行柱后光衍生化。新蝶呤(NEO)、生物蝶呤(BIO)、蝶呤(PT)和二氢生物蝶呤(BH2)通过测量天然荧光来测定,此时光反应器处于关闭模式;四氢生物蝶呤(BH4)通过测量生成的光产物的诱导荧光来测定,此时光反应器处于开启模式。此外,使用DAD检测器同时测定肌酐(CREA),作为尿液中代谢物排泄的参考指标。NEO、BH2、BIO、PT和BH4的检测限分别为0.2、13.0、0.3、0.3和3.5 ng mL-1,CREA的检测限为0.4 μg mL-1。报告了健康儿童和成人、苯丙酮尿症儿童和感染单核细胞增多症儿童尿液样本中NEO/CREA、PT/CREA、BH4/CREA、BH2/CREA、NEO/BIO和BIO(总量)/CREA的比值。对健康志愿者尿液样本采用本方法和经典碘氧化法(福岛法)测定每种化合物的平均值进行了比较研究。通过本方法得到的BH4/CREA、BH2/CREA和BIO(总量)/CREA的值分别为0.41、0.31和0.73,通过碘氧化法得到的值分别为0.35、0.20和0.48。