TDM of antiepileptics using minimally invasive methods - opportunities and challenges: determination of Lamotrigine in alternative matrices
| Autoři | |
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| Rok publikování | 2024 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Introduction Advanced analytical methods are precise and sensitive and allow the determination of substances at low concentrations in various biological matrices. An attractive application of these methods is determining drug levels in dry blood spots (DBS). However, practical feasibility is limited by several factors (low sample volume, matrix influence). Similarly, interpretation is hampered by the unclear relationship between capillary blood and plasma concentrations. This study aimed to develop and validate an analytical method for determining Lamotrigine in DBS and saliva and prove its correlation with LTG concentration assessed in plasma. Methods: The study was approved by the Ethics Committee of St. Anne's Hospital in Brno (Approval No. 3V/2023). The clinical samples (saliva, plasma, dried blood spots) were obtained from the patients of the 1st Neurological clinic of the St. Anne´s University Hospital Brno upon subscription of Informed consent. Sample preparation involved extraction, evaporation, and reconstitution in acetonitrile with formic acid. Kinetex C18 Polar column was used for separation, and MS/MS in ESI+ mode was used for LTG detection and quantitation. The method followed EMA guidelines for method validation, demonstrating accuracy, precision, selectivity, and stability. Results: A newly developed method enables the determination of Lamotrigine in dried blood spots and saliva. The validation in terms of precision and accuracy complied with EMA guidelines, with LLOQ in DBS of 1 µg/mL and LLOQ of 0.5 µg/mL in saliva. Linear regression and correlation between patient DBS and plasma samples was performed, with a correlation coefficient 0.994. Conclusions: The developed LC-MS method for LTG determination in DBS and saliva presents a promising alternative to traditional plasma analysis. Our results could contribute to the broader use of alternative matrix-based TDM methods, offering increased accessibility, improved adherence, and reduced stress for patients and caregivers. |
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