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. 2021 Jun 7;26(11):3470.
doi: 10.3390/molecules26113470.

Application of an LC-MS/MS Method for the Simultaneous Quantification of Homovanillic Acid and Vanillylmandelic Acid for the Diagnosis and Follow-Up of Neuroblastoma in 357 Patients

Narae Hwang  1 , Eunbin Chong  1 , Hyeonju Oh  1 , Hee Won Cho  2 , Ji Won Lee  2 , Ki Woong Sung  2 , Soo-Youn Lee  1   3   4
Affiliations

Application of an LC-MS/MS Method for the Simultaneous Quantification of Homovanillic Acid and Vanillylmandelic Acid for the Diagnosis and Follow-Up of Neuroblastoma in 357 Patients

Narae Hwang et al. Molecules. .

Abstract

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 r = 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.

Keywords: homovanillic acid; mass spectrometry; neuroblastoma; urine; validation; vanillylmandelic acid.

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Conflict of interest statement

The authors have no conflict of interests to declare.

Figures

Figure 1
Figure 1
Relationship between 1209 VMA and HVA concentrations in 357 patients.
Figure 2
Figure 2
Representative LC–MS/MS chromatograms of blank urine spiked with HVA (10 μg/mL), VMA (10 μg/mL), and their internal standards (HVA-d5 and VMA-d3, 5 μg/mL).
See this image and copyright information in PMC

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