Optimizing a High-Throughput Solid-Phase Microextraction System to Determine the Plasma Protein Binding of Drugs in Human Plasma

Plasma protein binding refers to the binding of a drug to plasma proteins after entering the body. The measurement of plasma protein binding is essential during drug development and in clinical practice, as it provides a more detailed understanding of the available free concentration of a drug in the blood, which is in turn critical for pharmacokinetics and pharmacodynamics studies. In addition, the accurate determination of the free concentration of a drug in the blood is also highly important for therapeutic drug monitoring and in personalized medicine. The present study uses C-18-coated solid-phase microextraction 96-pin devices to deter- mine the free concentrations of a set of drugs in plasma, as well as 30 45 the plasma protein binding of drugs with a wide range of physicochemical properties. It should be noted that the extracted amounts used to calculate the binding constants and plasma protein bindings should be measured at respective equilibrium for plasma and phosphate buffer. Therefore, special attention is placed on properly determining the equilibration times required to correctly estimate the free concentrations of drugs in the investigated systems. The plasma protein binding values obtained with the 96-pin devices are consistent with those reported in the literature. The 96-pin device used in this research can be easily coupled with a Concept96 or other automated robotic systems to create an automated plasma protein binding determination protocol that is both more time and labor efficient compared to conventional equilibrium dialysis and ultrafiltration methods.

Automated summary

Plasma protein binding refers to the binding of a drug to plasma proteins in the body, which is crucial for understanding the free concentration of a drug in the blood for pharmacokinetics and pharmacodynamics studies. Accurate determination of free drug concentrations in the blood is important for therapeutic drug monitoring and personalized medicine. The use of C-18-coated solid-phase microextraction 96-pin devices provides a more efficient method for determining plasma protein binding compared to traditional techniques.