Minimization of the preanalytical error in plasma samples for pharmacokinetic analyses and therapeutic drug monitoring--using doxorubicin as an example.

BACKGROUND There are many sources of variability in plasma samples drawn for pharmacokinetic analyses or therapeutic drug monitoring. In this article, methods are proposed on how to prevent sample dilution (Part I) and contamination effects (Part II) in plasma samples, using doxorubicin as an example. METHODS Experiments were performed in the laboratory setting to identify factors that could influence plasma samples in clinical practice. In part I, it was hypothesized that saline solution left in a catheter could lead to a dilution of samples drawn through this catheter. The impact of 2 different sampling techniques, the "discard method" and the "push-pull method", was examined. In part II, an infusion system was filled with a 1 mg/mL solution of doxorubicin. After rinsing the system with increasing volumes of saline solution, the drug concentration of the fluid left in the system was analyzed. Furthermore, plasma samples were drawn through the drug administration catheter, and the contamination of these samples with doxorubicin left in the catheter was measured. RESULTS In part I, a discard volume of plasma equal to 4 dead volumes of the sampling line was necessary to avoid dilution of a sample taken from a port or double-lumen catheter filled with saline solution ("discard method"). Pulling up and down the same volume through the catheter 5 times ("push-pull method") was proved to be an alternative with no need to discard blood. In part II, after rinsing the infusion system with a volume of saline solution corresponding to 4 dead volumes of the system and after discarding a volume of plasma corresponding to 4 sampling line volumes, the doxorubicin contamination in the samples was negligibly small. CONCLUSIONS Under the described conditions, the push-pull method delivered the same results as the discard method to prevent sample dilution. To avoid contamination in plasma samples, development of standardized sampling procedures seems to be essential and feasible.