HTC-15 - Abstract

Abstract Title: Solid Phase Micro-Extraction - Breaking Free from Total Concentration Analysis
Abstract Type: Seminar
Session Choice: Other
Presenter Name: Dr Sheelan Ahmad
Company/Organisation: GlaxoSmithKline
Country: United Kingdom

Abstract Information :

Drug molecules are either bound to plasma proteins (plasma protein binding) or are free (unbound) and can diffuse through biological membranes or bind to receptors. It is generally believed that the free concentration is the fraction which is responsible for causing a pharmacological response, only free drug molecules can interact with the therapeutic target and are available for distribution, elimination and other PK and PD actions. Hence, accurate determination of this parameter is essential for therapeutic drug monitoring, specifically for drugs with a narrow therapeutic window.

In this study the utility of BioSPME fibres for measuring free drug concentration from biological matrices was demonstrated both in vitro and in vivo. An in vitro experiment was conducted to compare the amount of drug extracted from protein free matrix (PBS) with the amount of drug determined from plasma (high protein content matrix). Three analytes were studied (metoprolol, propranolol and diclofenac) at three different concentrations (10, 100 and 500 ng/mL). The percentage of bound drug concentration extracted was then calculated and compared with values obtained using a conventional technique, rapid equilibrium dialaysis (RED) device, which is routinely utilised for establishing plasma drug protein binding. An in vivo study was also performed to determine the free concentration of metoprolol in conscious rats.

This presentation will give an overview of both studies and the potential of using SPME as a tool to measure free drug concentrations.