Spuriously low plasma propranolol concentrations resulting from blood collection methods

Area of Science:

• Pharmacology
• Clinical Chemistry
• Biomedical Analysis

Background:

• Accurate quantification of drug concentrations in biological samples is crucial for therapeutic drug monitoring.
• Variability in sample collection and processing can significantly impact assay results.
• Previous observations suggested potential interferences with drug measurements, but mechanisms were often unclear.

Purpose of the Study:

• To investigate the cause of spuriously low plasma propranolol concentrations observed with a specific commercial blood collection tube.
• To elucidate the mechanism behind the observed discrepancy in propranolol levels.
• To provide recommendations for reliable drug concentration analysis.

Main Methods:

• Comparative analysis of plasma propranolol concentrations using different collection tubes.
• Investigation of drug binding and redistribution in whole blood.
• Assessment of potential interfering substances in the collection tube stopper.

Main Results:

• A specific brand of blood collection tube was identified as the source of falsely low plasma propranolol values.
• The stopper of the collection tube contained substances that reduced plasma protein binding of propranolol.
• This led to a redistribution of propranolol, with higher concentrations found in red blood cells and lower concentrations in plasma.

Conclusions:

• The composition of blood collection tubes can significantly interfere with plasma drug concentration measurements.
• Routine validation of blood collection methods is essential to ensure accurate drug level determination.
• Using all-glass collection tubes or separate venipuncture can mitigate such interference.