Evaluation of low background liquid scintillation counter for non-clinical ADME studies

Abstract

1. The performance of low background (BG) liquid scintillation counter (LSC) was evaluated for practical purposes of non-clinical drug absorption, distribution, metabolism and excretion (ADME) studies. The measurement conditions for the radioactivity for low BG LSC were investigated and metabolite profiling in rat plasma after single oral administration of ¹⁴C-labeled compounds was performed. Metabolite profiling was also conducted using conventional LSC and accelerator mass spectrometer (AMS), and the performances of these measuring instruments were compared.

2. The established measurement conditions showed good linearity of the calibration curve over the concentration range from 3 to 300 dpm/vial. Metabolite profiling using low BG LSC for the plasma samples diluted to 5–55 times was comparable to that using conventional LSC for the undiluted plasma samples. Meanwhile, metabolite profiling using AMS for the plasma samples diluted to 250–2000 times was comparable to that using conventional LSC.

3. These results suggest that the application of low BG LSC is one of the useful tools for non-clinical ADME studies and that it is possible to select conventional LSC, low BG LSC or AMS for radioactivity measurement by considering the specific radioactivity of the compounds and the predicted concentrations of radioactivity in biological samples in ADME studies.

Keywords::

• LSC
• accelerator mass spectrometry
• AMS
• radioactivity measurement
• metabolite profiling
• drug development