Interference of Plasticizers on Plasma Protein Binding Measurements

Area of Science:

• Pharmacology
• Analytical Chemistry
• Biochemistry

Background:

• Accurate plasma protein binding (PPB) measurement is vital for drug discovery, especially for highly bound compounds.
• Evolving methodologies aim to improve PPB data quality, necessitating high-quality plasma and sensitive detection methods.
• Plasticizers leaching from polyvinyl chloride (PVC) bags can interfere with drug binding assays.

Purpose of the Study:

• To investigate the interference of plasticizers from PVC plasma storage bags on drug binding to human α1-acid glycoprotein (AAG) and human serum albumin (HSA).
• To compare plasma protein binding (PPB) measurements using plasma stored in PVC bags versus glass tubes.
• To identify optimal collection and storage methods for reliable PPB data.

Main Methods:

• Comparison of plasma fraction unbound (f_u,p) values for several AAG and HSA binding drugs.
• Blood and plasma were collected and stored using PVC bags or glass tubes via vacutainers.
• Evaluation of PPB in animal plasma collected using polypropylene syringes and polyethylene tubes.

Main Results:

• Plasma stored in PVC bags showed significantly higher f_u,p values compared to plasma stored in glass tubes, with differences up to 32-fold.
• Plasticizer interference was observed for certain drugs binding to AAG and HSA.
• Plasma from animal species collected using polypropylene syringes and polyethylene tubes did not show interference.

Conclusions:

• PVC plasma storage bags can introduce significant interference in PPB measurements due to plasticizer leaching.
• Vacutainers and glass tubes are recommended over PVC bags for blood collection and plasma storage to ensure accurate PPB data.
• Appropriate positive controls (e.g., warfarin for HSA, imatinib for AAG) are essential for monitoring plasma quality and minimizing plasticizer interference.