Measurement of 3-O-methyldopa from dried plasma microsamples by high-resolution mass spectrometry: A tool for the diagnosis of patients with high-risk neuroblastoma.

BACKGROUND

Risk assessment at diagnosis is crucial for neuroblastoma (NB) in order to address patients at high-risk to the most timely and appropriate treatments. 3-O-methyldopa (3-OMD), a direct metabolite of L-Dopa, is a promising biomarker of NB at diagnosis able to stratify high-risk patients.

METHODS

We show the development and validation of a method for measuring 3-OMD from dried plasma samples (DPS) and plasma using liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) on a Thermo Fisher Scientific Orbitrap Exploris 120.

RESULTS

The method was accurate and reproducible in the range 7.8-4000 ng/mL, from small amounts (50 mL) of plasma and DPS (obtained starting from 30 mL plasma). 3-OMD concentrations measured in plasma and DPS were highly correlated (R = 0.99 95 %CI 0.993-0.996). Differences of 3-OMD levels across stages L1 and M and L1 and L2 (p-value < 0.05) were statistically significant. Receiving Operator Curve (ROC) analysis showed that 3-OMD was able to discriminate patients at high-risk with high sensitivity and specificity both from plasma or DPS (AUC = 0.8295 %CI 0.71-0.94, P < 0.0001).

CONCLUSIONS

3-OMD is confirmed as an interesting biomarker of high-risk NB. The described method is an added value for further prospective studies involving multiple sites. The stability of 3-OMD in DPS allows for easy shipment and storage at room temperature.

Informations de copyright

Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.