Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
Molecules. 2021 Jun 7;26(11):3470. doi: 10.3390/molecules26113470.
Homovanillic acid (HVA) and vanillylmandelic acid (VMA) are end-stage metabolites of catecholamine and are clinical biomarkers for the diagnosis of neuroblastoma. For the first time in Korea, we implemented and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay to measure urinary concentrations of HVA and VMA according to Clinical and Laboratory Standards Institute guidelines. Our LC-MS/MS assay with minimal sample preparation was validated for linearity, lower limit of detection (LOD), lower limit of quantification (LLOQ), precision, accuracy, extraction recovery, carryover, matrix effect, and method comparison. A total of 1209 measurements was performed to measure HVA and VMA in spot urine between October 2019 and September 2020. The relationship between the two urinary markers, HVA and VMA, was analyzed and exhibited high agreement (89.1% agreement, kappa's k = 0.6) and a strong correlation (Pearson's = 0.73). To our knowledge, this is the first study to utilize LC-MS/MS for simultaneous quantitation of spot urinary HVA and VMA and analyze the clinical application of both markers on a large scale for neuroblastoma patients.
高香草酸（HVA）和香草扁桃酸（VMA）是儿茶酚胺的终末代谢产物，是神经母细胞瘤诊断的临床生物标志物。我们首次在韩国根据临床和实验室标准协会指南实施并验证了一种液相色谱串联质谱（LC-MS/MS）测定法，以测量尿液中 HVA 和 VMA 的浓度。我们的 LC-MS/MS 测定法具有最少的样品制备，可验证其线性、检测下限（LOD）、定量下限（LLOQ）、精密度、准确度、提取回收率、携带污染、基质效应和方法比较。总共进行了 1209 次测量，以在 2019 年 10 月至 2020 年 9 月之间测量点尿中的 HVA 和 VMA。分析了两种尿标志物 HVA 和 VMA 之间的关系，结果显示高度一致（89.1%一致，kappa's k = 0.6）和强相关性（Pearson's r = 0.73）。据我们所知，这是首次利用 LC-MS/MS 同时定量测定点尿中的 HVA 和 VMA，并对神经母细胞瘤患者的两种标志物进行大规模临床应用分析的研究。
