Determination of Unbound Fraction of Selected Antiepileptic Drug Using Ultrafiltration and LC-MS method
| Authors | |
|---|---|
| Year of publication | 2024 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Total plasma concentrations are commonly used for therapeutic drug monitoring of antiepileptic drugs (AED). On the other hand, drug activity and at least some of adverse effects depend on the unbound fraction of a drug in the bloodstream. The determination of free (unbound) concentrations by ultrafiltration is expected to reflect the effective drug concentration. Further, saliva is considered as a plasma ultrafiltrate, thus referring to free drug concentration. Therefore, the aim was to develop a method for the measurement of total and unbound AED concentrations in plasma and correlate them to saliva AED concentration. As a model drug, lamotrigine (LTG) was chosen since it is one of the most widely used AED and is moderately bound to albumin (~55% ). The samples of saliva and plasma were obtained from the patients treated at the Neurological clinic of the St. Anne´s Hospital, Brno upon subscription of Informed Consent. The study was approved by the Ethics Committee of St. Anne´s Hospital in Brno (Approval No. 3V/2023). The plasma samples for the determination of unbound LTG concentrations were processed by ultrafiltration and liquid-liquid extraction by ethyl acetate. The same extraction step was performed for plasma and saliva samples too. The extraction efficiency of LTG and its internal standard (LTG-13C15N4) was about 90 % for all matrices. All LTG plasma concentrations were within the recommended therapeutical range (3-15 ug/ml). Pilot data show that the concentrations measured in plasma ultrafiltrate and saliva were in close proximity, even though total plasma concentrations are much higher and wildly differ between individual samples. More data must be available to determine the correlation between saliva and plasma concentrations and saliva and ultrafiltrate concentrations. |
| Related projects: |