Measurement of Centanafadine Concentrations in a Pharmacokinetic Trial: Comparison of Traditional Venipuncture Versus...

In clinical pharmacology trials, pharmacokinetic samples are typically collected via venipuncture by trained staff. However, recent advances in blood collection devices have enabled participant self-collection of samples. Here, we describe the feasibility of collecting dried blood from healthy volunteers using a microsampling device by comparing centanafadine concentrations from self-collected microsamples with those collected via venipuncture by phlebotomists in an exploratory phase 1 pharmacokinetic trial. High-performance liquid chromatography with tandem mass spectrometric (HPLC-MS/MS) bioanalytical methods were validated for both dried blood collected via microsampling and plasma, with all validation criteria successfully met. Concordance between venous and microsamples was evaluated using graphical analysis and Deming regression, based on data from two conventional phase 1 trials (samples collected by clinical staff) and an exploratory pharmacokinetic trial comparing staff-collected venous samples (visits 1 and 2) with microsamples collected by staff (visit 1) or self-collected by participants (visits 2 and 4). Deming regression revealed significant linear relationships between centanafadine concentrations from venous and dried blood samples in conventional trials, and between microsamples at visits 2 and 4 versus visit 1 in the exploratory pharmacokinetic trial (visit 2: self-collected under supervision, slope = 1.135; visit 4: self-collected at home, slope = 0.967). The bioanalytical method used for the measurement of centanafadine concentrations in dried blood collected by the microsampling device was successfully validated, and feasibility assessments resulted in concordance suggesting that it is suitable to collect centanafadine pharmacokinetic samples at home during the conduct of self-collection phase 1 pharmacokinetic trials.