Journal
BIOANALYSIS
Volume 4, Issue 9, Pages 1077-1095Publisher
FUTURE SCI LTD
DOI: 10.4155/BIO.12.85
Keywords
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Funding
- Pfizer Worldwide RD (CA, USA)
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Background: Initial pharmacokinetic (PK) studies of discovery compounds are conducted in mice to demonstrate exposure prior to conducting efficacy studies. PK information obtained from a single mouse by serial blood microsampling, dried blood spot collection and analyses using microbore (1 mm internal diameter column) LC-MS/MS is presented. Ex vivo blood to plasma concentration ratios (BPRs) from mouse PK studies were compared with in vitro BPRs for 15 compounds. Results: Two compounds were orally dosed and blood was collected at time points via serial blood sampling. The calculated PK parameters (AUC, T-max and C-max) were comparable across liquid blood, dried blood spot and plasma matrices. The BPR results from both methods were comparable. Conclusion: Serial blood microsampling has led to reduced animal and compound usage with improved PK data. Ex vivo BPR is suitable in a discovery setting. Microbore LC-MS/MS is well suited in instances where sample volume is limited, and enables faster analyses, reduced solvent use, and less frequent MS source cleaning.
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