Drug-protein binding interferences caused by the plasticizer TBEP

Area of Science:

• Pharmacology
• Analytical Chemistry
• Biochemistry

Background:

• Tris (2-butoxyethyl) phosphate (TBEP) is a plasticizer found in blood collection tube stoppers.
• TBEP is known to interfere with drug-protein binding, specifically to alpha-1-acid glycoprotein (AAG).
• This interference can impact the accuracy of therapeutic drug monitoring (TDM).

Purpose of the Study:

• To investigate the effect of TBEP on the serum levels of basic drugs.
• To quantify the impact of TBEP on drug-protein binding and free drug concentrations.
• To assess the influence of AAG levels on TBEP's effect.

Main Methods:

• Blood samples were spiked with quinidine or lidocaine.
• Samples were exposed to blood collection tube stoppers with and without TBEP.
• Total and free drug levels were measured using enzyme immunoassay and equilibrium dialysis.
• Alpha-1-acid glycoprotein (AAG) levels were determined by rate nephelometry.

Main Results:

• TBEP significantly reduced quinidine and lidocaine serum levels.
• TBEP exposure increased the percentage of free lidocaine from 66.7% to 80.0%.
• The observed TBEP effect was less pronounced at lower AAG concentrations.

Conclusions:

• TBEP in blood collection tubes can lead to falsely decreased serum drug levels.
• Disruption of drug-AAG binding by TBEP affects TDM accuracy for basic drugs.
• Monitoring AAG levels may be important when interpreting TDM results from samples potentially exposed to TBEP.