Abstract
Microsampling contributes to 3Rs (Replacement, Reduction and Refinement) of animals and it also enables to evaluate the relationship directly between the safety data and drug exposure in the same animal. Previously, much sampling blood volume was required for the determination of drugs in TK analysis, but recent progress in sensitivity of analytical instruments contributed to the spread of the sample reducing technique. As Q & A for S3A guideline in Japanese version “QUESTIONS AND ANSWERS TO ICH S3A: NOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT OF SYSTEMIC EXPOSURE IN TOXICITY STUDIES FOCUS ON MICROSAMPLING” was issued from MHLW in March 2019, it is likely to spread from now on.
Next generation pharmaceuticals are increasingly used in drug development worldwide. Among them, oligonucleotide therapeutics is a typical new modality that is continuously launched from around 2016 and also likely to be developed from now on.
We focused on oligonucleotide therapeutics because relatively less number of microsampling applications are reported in the field. Nusinersen is antisense oligonucleotides for spinal muscular atrophy treatment. In order to determine Nusinersen concentration in rat plasma obtained by microsampling, a determination method was developed using peptide adsorption-controlled-LC (PAC-LC) 1) combined with a mass spectrometer. Actual determination results of Nusinersen concentration in rat plasma obtained by microsampling are also reported including incurred sample reanalysis (ISR).
1) Goda R., Sudo K., Biomed. Chromatogr., 21, 1005-1015 (2007)
