Publication details
Free Drug Concentrations in Plasma: Optimization of Ultrafiltration and Validation of an LC-MS Method for Clinical Purposes
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| Year of publication | 2026 |
| Type | Conference abstract |
| Citation | |
| Description | Determination of the free drug concentration in plasma has great importance in clinical pharmacology, as the unbound fraction provides more accurate information about the actual pharmacological effect (i.e. drug efficacy and safety). The most useful fluid for estimating free drug concentrations appears to be plasma or serum, with subsequent treatment of the sample to separate free and bound drug by an appropriate technique. The two most widely used methods are equilibrium dialysis and ultrafiltration. Of these two, ultrafiltration has the greatest clinical utility because it is rapid and relatively simple. This study aimed to optimize centrifugation parameters for plasma ultrafiltration, validate a robust LC-MS/MS method for quantifying the free fractions of the antiepileptic drugs lamotrigine (LTG) and valproate (VPA), and apply the optimized workflow to clinical samples from epilepsy patients. The optimized ultrafiltration protocol was successfully integrated into the pre-analytical sample preparation workflow, ensuring precise separation of the unbound drug fraction without compromising membrane integrity. Coupled with the validated LC-MS/MS method, this optimized methodology provides a robust, high-throughput platform for the accurate quantification of free LTG and VPA concentrations in clinical plasma samples. Consequently, the free VPA concentration data will be directly applied to the subsequent phases of the project focused on determination of the drug in different biological matrices. |
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