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- Title
ULTRAFILTRATION METHOD FOR PLASMA PROTEIN BINDING DETERMINATION - ADVANTAGES AND LIMITATIONS.
- Authors
Camelia-Maria, Toma; Echim, Iulia; Silvia, Imre; Camil-Eugen, Vari
- Abstract
Background: Plasma protein binding (PPB) has a critical role in both pharmacokinetics and pharmacodynamics of a drug, being amongst other properties like lipophilicity, solubility, ionization and metabolic behavior a key part in the characterization of a new compound, which should be studied in the early stages of drug development. Objective: The aim of the study was to underline key aspects regarding practical strategies for PPB determination. Material and methods: Scientific literature research on platforms such as PubMed, Science Direct, Medline and systematic analysis. Results: One of the most used methods is ultrafiltration, which is largely accepted due to its advantages: rapidity, simplicity, accuracy, the possibility of approximating physiological conditions. Ultrafiltration has, however, some disadvantages which could limit its use, so it is of great importance to know and understand how to overcome them. Nonspecific binding of the drug to the filter membrane or the ultrafiltration unit represents one of the biggest challenges in PPB studies, especially for lipophilic compounds. Several studies were made to overcome this limitation and encouraging results were obtained: pre-treatment of the ultrafiltration units with solutions of Tweens or benzalkonium chloride; incubation and the ultrafiltration device in plasma followed by a mass balance approach to determine the recovery of the drug; slight modifications of the classical ultrafiltration technique. The effect of volume ratio of the ultrafiltrate to the sample solution was also considered as a limitation, but more recent studies have stated that this was only a misunderstanding. Other limitations: sieve effect, Gibbs- Donnan effect, protein leakage and the necessity of a rigorous control of the temperature and pH. Conclusions: Ultrafiltration remains a reliable method for the determination of PPB, even in the case of more challenging compounds, but the methodology of the study should be carefully chosen based on the properties of each analyte in order to overcome the limitations, and subsequently validated.
- Subjects
BLOOD proteins; PROTEIN binding; ULTRAFILTRATION; SCIENTIFIC literature; MEMBRANE filters
- Publication
Acta Medica Marisiensis, 2019, Vol 65, p56
- ISSN
2068-3324
- Publication type
Article