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Title:An LC-MS/MS method for quantification of lamotrigine and its main metabolite in dried blood spots
Authors:ID Milosheska, Daniela (Author)
ID Roškar, Robert (Author)
ID Vovk, Tomaž (Author)
ID Lorber, Bogdan (Author)
ID Grabnar, Iztok (Author)
ID Trontelj, Jurij (Author)
Files:.pdf PDF - Presentation file, download (2,87 MB)
MD5: CA6DA12A4BC76D6FD2F8E3C8F133899F
 
URL URL - Source URL, visit https://www.mdpi.com/1424-8247/17/4/449
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo UKC LJ - Ljubljana University Medical Centre
Abstract:Background: The antiepileptic drug lamotrigine (LTG) shows high pharmacokinetic variability due to genotype influence and concomitant use of glucuronidation inducers and inhibitors, both of which may be frequently taken by elderly patients. Our goal was to develop a reliable quantification method for lamotrigine and its main glucuronide metabolite lamotrigine-N2-glucuronide (LTG-N2-GLU) in dried blood spots (DBS) to enable routine therapeutic drug monitoring and to identify altered metabolic activity for early detection of drug interactions possibly leading to suboptimal drug response. Results: The analytical method was validated in terms of selectivity, accuracy, precision, matrix effects, haematocrit, blood spot volume influence, and stability. It was applied to a clinical study, and the DBS results were compared to the concentrations determined in plasma samples. A good correlation was established for both analytes in DBS and plasma samples, taking into account the haematocrit and blood cell-to-plasma partition coefficients. It was demonstrated that the method is suitable for the determination of the metabolite-to-parent ratio to reveal the metabolic status of individual patients. Conclusions: The clinical validation performed confirmed that the DBS technique is a reliable alternative for plasma lamotrigine and its glucuronide determination.
Keywords:dried blood spot, lamotrigine, lamotrigine glucuronide, therapeutic drug monitoring, clinical validation, haematocrit effect
Publication status:Published
Publication version:Version of Record
Year of publishing:2024
Number of pages:16 str.
Numbering:Vol. 17, no. 4, [Article no.] 449
PID:20.500.12556/DiRROS-30161 New window
UDC:615.015:616.853
ISSN on article:1424-8247
DOI:10.3390/ph17040449 New window
COBISS.SI-ID:191424771 New window
Note:Nasl. z nasl. zaslona; Opis vira z dne 4. 4. 2024;
Publication date in DiRROS:16.06.2026
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Downloads:15
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Record is a part of a journal

Title:Pharmaceuticals
Shortened title:Pharmaceuticals
Publisher:MDPI, Molecular Diversity Preservation International
ISSN:1424-8247
COBISS.SI-ID:517582617 New window

Document is financed by a project

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P1-0189-2018
Name:Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

Language:Slovenian
Keywords:posušena krvna lisa, lamotrigin, lamotrigin glukuronid, terapevtsko spremljanje zdravil, klinična validacija, učinek hematokrita


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