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Chromatographic Characterization and Method Development for Determination of Levetiracetam in Saliva: Application to
Imad I Hamdan1, Mervat Alsous2, Amira Taher Masri3
1School of Pharmacy, The University of Jordan, Amman, Jordan.
Insights
Saliva can be used for therapeutic drug monitoring of levetiracetam (LVT) in children. This study developed a simple HPLC method showing good correlation between saliva and plasma LVT levels, aiding patient compliance assessment.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Pediatrics
Background:
- Levetiracetam (LVT) is a common antiepileptic drug (AED).
- Therapeutic drug monitoring (TDM) is crucial for AEDs, especially in children.
- Less invasive sampling methods for TDM are needed.
Purpose of the Study:
- To develop and validate a simple, isocratic HPLC method for determining LVT in saliva.
- To assess the correlation between salivary and plasma LVT levels for TDM.
- To investigate patient compliance in epileptic children.
Main Methods:
- Examined LVT retention on various stationary phases, identifying C8 as most retentive.
- Developed a simple isocratic HPLC method using protein precipitation for saliva sample preparation.
- Validated the developed method for LVT determination in saliva.
Main Results:
- A reasonable correlation (R=0.9) was found between plasma and salivary LVT levels.
- The developed HPLC method is suitable for salivary TDM of LVT.
- A significant percentage of epileptic patients showed LVT levels below the therapeutic range.
Conclusions:
- Saliva is a viable alternative to plasma for LVT TDM in children.
- The developed HPLC method facilitates easier TDM and compliance monitoring.
- Findings highlight potential issues with LVT dosing or adherence in pediatric epilepsy patients.
Abstract:
Levetiracetam (LVT) is a widely used antiepileptic drug (AED). A less invasive sampling method for therapeutic drug monitoring (TDM) would be very useful particularly for children. Saliva has been shown as an adequate sample for TDM of some AEDs. Due to the high hydrophilicity of LVT its separation on common stationary phases is quite a challenge so that previous methods for determination of LVT in saliva employed either gradient high performance liquid chromatographic (HPLC) system or mass spectrometer as a detector. In this study the retention behavior of LVT on some common stationary phases was examined, with C8 being the most retentive. A simple isocratic HPLC method that is based on simple protein precipitation was developed and validated for the determination of LVT in saliva. The method was applied to a sample group of epileptic children for the purpose of assessing potential correlation with plasma LVT levels and to investigate patient's compliance. The results confirmed a reasonable correlation between plasma and salivary levels of LVT (R = 0.9) which supports the use of saliva for TDM of LVT. The study also revealed a significant percentage of epileptic patients having LVT levels below the estimated therapeutic range.
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