TY - JOUR
T1 - Validation of an LC-MS/MS method for urinary homovanillic and vanillylmandelic ACIDS and application to the diagnosis of neuroblastoma
AU - Rossi, Lucilla
AU - Matser, Yvette A H
AU - Barco, Sebastiano
AU - Cafaro, Alessia
AU - Pigliasco, Federica
AU - Biondi, Margherita
AU - Mancin, Fabrizio
AU - van der Ham, Maria
AU - de Sain-van der Velden, Monique G M
AU - Ash, Shifra
AU - Popovic, Maja Beck
AU - van Kuilenburg, André B P
AU - Conte, Massimo
AU - Garaventa, Alberto
AU - Tytgat, Godelieve A M
AU - Cangemi, Giuliana
N1 - Publisher Copyright:
© 2025
PY - 2025/4
Y1 - 2025/4
N2 - BACKGROUND: Urinary catecholamine metabolites are well-established biomarkers for neuroblastoma (NB). Homovanillic acid (HVA) and vanillylmandelic acid (VMA) are the most frequently measured metabolites within SIOPEN - Catecholamine Working Group laboratories. Here, we evaluated the performance of a new LC-MS/MS in vitro diagnostic (IVD) kit for HVA and VMA to facilitate inter-laboratory harmonization.METHODS: HVA and VMA and their deuterated internal standards were analyzed with a commercial method, on a ThermoFisher Quantiva LC-MS/MS. Validation was performed first using internal quality control and external quality assessment (IQC and EQA) samples. Next by clinical validation on 120 samples, previously tested by HPLC-ECD. Finally, 36 samples were exchanged between SIOPEN reference laboratories and analyzed by three methods.RESULTS: Using QCs and EQA the method was validated in a wide calibration range (4.61-830 µmol/L for HVA and 4.44-800 µmol/L for VMA). Intra-day CVs (
n = 5) were 7 and 8 % for HVA and 5 and 6 % for VMA for QC low and QC high, respectively; Inter-day CV% were 7 and 3 % for HVA and 2 and 7 % for VMA at QC low and QC high, respectively. Its application to 120 clinical samples confirmed a high diagnostic accuracy. The inter-laboratory quality control assessment showed interchangeable results (
p = 0,73 and
p = 0.15 for HVA and VMA, respectively).
CONCLUSION: The LC-MS/MS IVD method could be considered a useful tool for clinical laboratories involved in the measurement of catecholamines, contributing to harmonization efforts.
AB - BACKGROUND: Urinary catecholamine metabolites are well-established biomarkers for neuroblastoma (NB). Homovanillic acid (HVA) and vanillylmandelic acid (VMA) are the most frequently measured metabolites within SIOPEN - Catecholamine Working Group laboratories. Here, we evaluated the performance of a new LC-MS/MS in vitro diagnostic (IVD) kit for HVA and VMA to facilitate inter-laboratory harmonization.METHODS: HVA and VMA and their deuterated internal standards were analyzed with a commercial method, on a ThermoFisher Quantiva LC-MS/MS. Validation was performed first using internal quality control and external quality assessment (IQC and EQA) samples. Next by clinical validation on 120 samples, previously tested by HPLC-ECD. Finally, 36 samples were exchanged between SIOPEN reference laboratories and analyzed by three methods.RESULTS: Using QCs and EQA the method was validated in a wide calibration range (4.61-830 µmol/L for HVA and 4.44-800 µmol/L for VMA). Intra-day CVs (
n = 5) were 7 and 8 % for HVA and 5 and 6 % for VMA for QC low and QC high, respectively; Inter-day CV% were 7 and 3 % for HVA and 2 and 7 % for VMA at QC low and QC high, respectively. Its application to 120 clinical samples confirmed a high diagnostic accuracy. The inter-laboratory quality control assessment showed interchangeable results (
p = 0,73 and
p = 0.15 for HVA and VMA, respectively).
CONCLUSION: The LC-MS/MS IVD method could be considered a useful tool for clinical laboratories involved in the measurement of catecholamines, contributing to harmonization efforts.
U2 - 10.1016/j.jmsacl.2025.04.007
DO - 10.1016/j.jmsacl.2025.04.007
M3 - Article
C2 - 40421176
SN - 2667-145X
VL - 36
SP - 73
EP - 81
JO - Journal of mass spectrometry and advances in the clinical lab
JF - Journal of mass spectrometry and advances in the clinical lab
ER -