Bioanalysis for Plasma Protein Binding Studies in Drug Discovery and Drug Development: Views and Recommendations of The European Bioanalysis Forum

Figures & data

Figure 1. Answers provided to the question: “Do you qualify/validate a method before analysis of PPB samples?” The question was asked in three surveys.

(A) Survey I: PPB in drug-discovery phase. (B) Survey II: in vitro PPB in drug-development phase. (C) Survey III: in vivo PPB in drug-development phase.

PPB: Plasma protein binding.

Table 1. Plasma protein binding techniques selected based on compound characteristics.

Technique	Highly lipophilic	Highly hydrophilic	Biologicals	Labile	Sticky
Answers to survey II: in vitro plasma protein binding
Ultrafiltration	++	+++++		+++++	+
Equilibrium dialysis	++++	+++++			+
Ultracentrifugation	++		+	+	+++
Transil™ partitioning	+				+
Gel filtration	+				+
Answers to survey IIl: in vitro plasma protein binding
Ultrafiltration		+		+++
Equilibrium dialysis	++	++
Ultracentrifugation					+
Transil partitioning	+				+

Answers were obtained from the survey regarding in vitro plasma protein binding studies (upper table) and in vivo plasma protein binding studies (lower table) in drug-development phase.

The number of symbols indicate if the technique is used by many companies (greater number of symbols) or by just a few companies (smaller number of symbols).

Table 2. Plasma protein binding techniques selected based on anticipated protein binding: very high protein binding (>98%), high protein binding (85–98%) and medium to low protein binding (<85%).

Technique	Very high (>98%)	High (85–98%)	Medium to low (<85%)
Answers to survey II: in vitro plasma protein binding
Ultrafiltration			++++
Equilibrium dialysis	+++	+++++	++
Ultracentrifugation	+	+
Transil™ partitioning	+
Gel filtration	+
Answers to survey IIl: in vitro plasma protein binding
Ultrafiltration			+
Equilibrium dialysis	+	++	+
Ultracentrifugation	+	+
Transil partitioning	+

Answers were obtained from the survey regarding in vitro plasma protein binding studies (upper table) and in vivo plasma protein binding studies (lower table) in drug-development phase.

The number of symbols indicate if the technique is used by many companies (greater number of symbols) or by just a few companies (smaller number of symbols).