Drug-protein binding interferences caused by the plasticizer TBEP

Tris (2-butoxyethyl) phosphate (TBEP) is a plasticizer used in the rubber stoppers of evacuated blood collection tubes which disrupts the binding of basic drugs to the carrier protein alpha-1-acid glycoprotein (AAG). When blood drawn for therapeutic monitoring is exposed to TBEP, drug-protein binding is disrupted leading to increased free drug which is taken into red blood cells, resulting in decreased serum drug levels. Units of donor blood were spiked with quinidine or lidocaine and then exposed under various conditions to stoppers with and without TBEP. Total drug levels were determined by enzyme immunoassay as were free drug levels after equilibrium dialysis. AAG levels were determined by rate nephelometry. TBEP lowered quinidine levels by 11% at 8.20 mumol/L and by 32% at 4.38 mumol/L; lidocaine levels were reduced by 10% at 32.39 mumol/L and by 18% at 12.74 mumol/L. Exposure to TBEP increased free lidocaine from 66.7% to 80.0% of total lidocaine in the serum. The TBEP effect is diminished when the AAG level is low.