Simultaneous determination of four antiepileptic drugs in human plasma samples using an ultra-high-performance liquid chromatography tandem mass spectrometry method and its application in therapeutic drug monitoring
| Autor: | Natalia Doudka, Romain Guilhaumou, Julien Dupouey, Séphora Belo, Olivier Blin |
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| Rok vydání: | 2016 |
| Předmět: |
Metabolite
Clinical Biochemistry Pharmacology Tandem mass spectrometry 030226 pharmacology & pharmacy 01 natural sciences Biochemistry Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Liquid chromatography–mass spectrometry Drug Discovery medicine Protein precipitation Oxcarbazepine Molecular Biology Active metabolite Detection limit Chromatography medicine.diagnostic_test 010401 analytical chemistry General Medicine 0104 chemical sciences chemistry Therapeutic drug monitoring medicine.drug |
| Zdroj: | Biomedical Chromatography. 30:2053-2060 |
| ISSN: | 0269-3879 |
| DOI: | 10.1002/bmc.3789 |
| Popis: | Therapeutic drug monitoring of antiepileptic drugs is widely practiced to achieve optimal efficacy and avoid adverse side effects. We describe an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC/MS/MS) method developed for the monitoring of four frequently prescribed antiepileptic drugs - lamotrigine, levetiracetam, oxcarbazepine and topiramate. The main pharmacologically active metabolite of oxcarbazepine (mono-hydroxy-derivative metabolite, MHD) was also quantified. After addition of internal standards and a simple stage of protein precipitation, plasmatic samples were analyzed on a C18 column. All antiepileptic drugs were separated and quantified in 6 min, without interference. A good linearity was observed all over the calibration range (r2 > 0.99), up to 20 μg/mL (40 μg/mL for MHD). The limit of quantification was 0.20 μg/mL (0.40 μg/mL for MHD) with precision and accuracy ranging from 1.0 to 2.1% and from 96.7 to 110.8%, respectively. Intra- and inter-day precision and accuracy values were within 15%. No significant matrix effect was observed for all analytes. Clinical application was successfully evaluated in 259 samples from patients treated for epilepsy or bipolar disorders. In conclusion, a rapid, specific and sensitive UHPLC/MS/MS method was developed and validated for simultaneous quantification of antiepileptic drugs, suitable for therapeutic drug monitoring in neurology and psychiatry. |
| Databáze: | OpenAIRE |
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