An LC-MS/MS method for quantification of lamotrigine and its main metabolite in dried blood spots

Milosheska, Daniela (author), Roškar, Robert (author), Vovk, Tomaž (author), Lorber, Bogdan (author), Grabnar, Iztok (author), Trontelj, Jurij (author)

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.

• Language: English
• Keywords: dried blood spot, lamotrigine, lamotrigine glucuronide, therapeutic drug monitoring, clinical validation, haematocrit effect
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 16 str.
• Numbering: Vol. 17, art. 449
• PID: 20.500.12556/RUL-155604
• UDC: 615.015:616.853
• ISSN on article: 1424-8247
• DOI: 10.3390/ph17040449
• COBISS.SI-ID: 191424771
• Publication date in RUL: 08.04.2024

Record is a part of a journal

• Title: Pharmaceuticals
• Shortened title: Pharmaceuticals
• Publisher: MDPI
• ISSN: 1424-8247
• COBISS.SI-ID: 517582617

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: epileptični napadi, farmakokinetika, posušena krvna lisa, lamotrigin, lamotrigin glukuronid, terapevtsko spremljanje zdravil, klinična validacija, učinek hematokrita

Projects

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

• Funder: Other - Other funder or multiple funders
• Funding programme: Ad Futura Scientific and Educational Foundation of the Republic of Slovenia