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.
Biomed Chromatogr
; 30(12): 2053-2060, 2016 Dec.
Article
en En
| MEDLINE
| ID: mdl-27417975
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cromatografía Líquida de Alta Presión
/
Monitoreo de Drogas
/
Espectrometría de Masas en Tándem
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Anticonvulsivantes
Tipo de estudio:
Guideline
Límite:
Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article