A novel UPLC-MS-MS method for simultaneous determination of seven uremic retention toxins with cardiovascular relevance in chronic kidney disease patients
A novel UPLC-MS-MS method for simultaneous determination of seven uremic retention toxins with cardiovascular relevance in chronic kidney disease patients
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DOI：
10.1007/s00216-012-6636-9
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发表时间：
2013-02-01
影响因子：
4.3
通讯作者：
Vanholder, Raymond
中科院分区：
文献类型：
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作者：
Boelaert, Jente;Lynen, Frederic;Vanholder, Raymond
慢性肾脏病（CKD）是一种破坏性疾病，其特征是尿毒症滞留溶质在体内的积累。本研究的目的是建立并验证一种简单、快速、耐用的UPLC-MS-MS方法，用于同时测定血清中7种有机酸尿毒症潴留毒素，即尿酸（UA）、马尿酸（HA）、吲哚硫酸酯（IS）、对甲苯基葡萄糖醛酸苷（pCG）、对甲苯基硫酸酯（pCS）、吲哚-3-乙酸（IAA）、和3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF）。同位素标记的内标物（d（5）-HA; 1，3-N-15（2）-UA和d（5）-IAA）用于校正样品制备和系统性能的变化。在C18柱上分离，然后通过负电喷雾电离和串联质谱检测。准确度低于15%阈值。所有化合物的日内精密度为0.60 - 4.54%，日间精密度低于13.33%。通过分析78份来自健康对照和不同阶段CKD患者的血清样本，评估了该方法的适用性。这些结果进行了比较，通过使用传统的HPLC-PDA-FLD方法获得的结果。所有化合物的两种方法之间获得了良好的相关性。
Chronic kidney disease (CKD) is a devastating illness characterized by accumulation of uremic retention solutes in the body. The objective of this study was to develop and validate a simple, rapid, and robust UPLC-MS-MS method for simultaneous determination, in serum, of seven organic acid uremic retention toxins, namely uric acid (UA), hippuric acid (HA), indoxylsulfate (IS), p-cresylglucuronide (pCG), p-cresylsulfate (pCS), indole-3-acetic acid (IAA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). Isotopically labeled internal standards (d(5)-HA; 1,3-N-15(2)-UA, and d(5)-IAA) were used to correct for variations in sample preparation and system performance. Separation on a C18 column was followed by negative electrospray ionization and tandem mass spectrometric detection. Accuracy was below the 15 % threshold. Within-day precision varied from 0.60 to 4.54 % and between-day precision was below 13.33 % for all compounds. The applicability of the method was evaluated by analyzing 78 serum samples originating both from healthy controls and from patients at different stages of CKD. These results were compared with those obtained by use of conventional HPLC-PDA-FLD methods. A good correlation was obtained between both methods for all compounds.