Impact of hemolysis during sample collection: How different is drug concentration in hemolyzed plasma from that of normal plasma?

Hemolysis is a common phenomenon in clinical studies. Despite the growing interest in hemolysis matrix effect, how hemolysis impacts the representability of hemolyzed plasma samples was rarely evaluated. The purpose of this research is to perform such an evaluation by theoretical consideration and experiment. A formula for estimating the impact is proposed, which includes the degree of hemolysis and the drug's red blood cell (RBC): plasma concentration ratio. The impact of hemolysis on the representability of hemolyzed plasma samples is compound-dependant. Given the same degree of hemolysis, the stronger a drug binds to RBCs, the more significant the impact of hemolysis. For a drug with high affinity to RBCs, the results of hemolyzed plasma samples may not be useful even though they are accurate. There is an overall agreement between theoretical predication and experimental results. Among the ten different drug compounds tested, only methazolamide, which binds strongly to RBCs, showed significant change in plasma concentration due to hemolysis.

► Systematic evaluation of hemolysis impact on drug sequestration in plasma.
► Proposed a formula for estimating the impact for the first time.
► Hemolysis could impact the representability of hemolyzed plasma samples.
► The impact is compound-dependent.
► Evaluating hemolysis matrix effect only is not enough for hemolyzed plasma samples.