RT Journal Article
T1 Development and application of an LC-MS/MS method for 8 antiepileptic drugs and 2 metabolites using microsampling techniques (DBS and VAMS)
A1 Cobo Golpe, María
A1 Paniagua González, Lucía
A1 Lendoiro Belío, Elena
A1 Blanco-Ces, Miriam
A1 López Rabuñal, Ángela
A1 López-Rivadulla Lamas, Manuel
A1 Cruz Landeira, Angelines
A1 Castro Ríos, Ana de
K1 Antiepileptic drugs
K1 Dried blood spots (DBS)
K1 LC-MS/MS
K1 Therapeutic drug monitoring
K1 Volumetric absorptive microsampling (VAMS)
AB Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is used for optimization and individualization of patients′ treatment. Capillary microsampling techniques are a promising alternative to conventional venous sampling for TDM. Both dried blood spots (DBS) and volumetric adsorptive microsampling (VAMS) devices are less invasive and patient-friendly sampling techniques which have been gaining interest in the last years. This study describes the development and validation of an LC-MS/MS method for the determination of 8 AEDs (Carbamazepine, Lacosamide, Levetiracetam, Lamotrigine, Phenobarbital, Valproic acid) and 2 metabolites (10,11-Dihydro-10-hydroxy-carbamazepine (DHCB) and carbamazepine-10,11-epoxide) in DBS and VAMS samples. The method was fully validated for linearity, selectivity, accuracy, precision, carryover, matrix effect, recovery and stability (15days at room temperature and 72h in autosampler). Moreover, the volume effect, volcano effect, and the hematocrit (Hct) effect were also assessed for DBS samples. All parameters showed satisfactory results, with a limit of quantification ranging from 0.5 to 10µg/mL, depending on the analyte. Some instability issues were detected in DBS samples for oxcarbazepine. However, the inclusion of oxcarbazepine’s metabolite DHCB overcomes this problem as it was stable under both conditions tested. Moreover, this is the first DBS or VAMS method reporting the inclusion of DHCB, which seems essential for the TDM of oxcarbazepine. The method was applied to 80 paired samples from patients under treatment with these drugs in order to study the suitability of the method for the detection of these compounds, and compare concentrations in paired VAMS, DBS, whole blood and plasma samples. Ratios between paired samples show a promising correlation between microsampling techniques and plasma concentrations.
PB Oxford University Press
SN 0146-4760
YR 2025
FD 2025-07-16
LK https://hdl.handle.net/10347/43067
UL https://hdl.handle.net/10347/43067
LA eng
NO María Cobo-Golpe, Lucía Paniagua-González, Elena Lendoiro, Miriam Blanco-Ces, Ángela López-Rabuñal, Javier Abella, Dolores Castro, Cristina Melcón, Patricia Fuentes, Iria Carballeira, Carlos García, Carmen Gómez, Manuel López-Rivadulla Lamas, Angelines Cruz, Ana de-Castro-Ríos, Development and application of an LC-MS/MS method for 8 antiepileptic drugs and 2 metabolites using microsampling techniques (DBS and VAMS), Journal of Analytical Toxicology, 2025;, bkaf073, https://doi.org/10.1093/jat/bkaf073
NO This publication is part of the R&D&I project PID2021- 124286OB-I00, financed by MCIN/AEI/10.13039/501100011033/ and by “ERDF A way of making Europe.” Plan Nacional sobre Drogas, Ministerio de Sanidad, Gobierno de España, for her contract (grant EXP2022/008675, financed by European Union NextGenerationEU/PRTR).
DS Minerva
RD 27 abr 2026