Discovery pharmacokinetic studies in mice using serial microsampling, dried blood spots and microbore LC-MS/MS
| Autor: | Leslie Nguyen, Bhasker Shetty, Minerva R. Batugo, Heather Skor, Zhongzhou Shen, Sylvia Vekich, Sadayappan V. Rahavendran |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Pyridines Clinical Biochemistry Cmax Drug Evaluation Preclinical Pharmacology Mass Spectrometry Piperazines Analytical Chemistry Mice Plasma Pharmacokinetics Crizotinib Lc ms ms Animals General Pharmacology Toxicology and Pharmaceutics Chromatography High Pressure Liquid Dried Blood Spot Testing Blood Specimen Collection Mice Inbred BALB C Chromatography Spots Chemistry General Medicine Dried blood spot Medical Laboratory Technology Pharmaceutical Preparations Isotope Labeling Pyrazoles Ex vivo Blood sampling |
| Zdroj: | Bioanalysis. 4(9) |
| ISSN: | 1757-6199 |
| Popis: | 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, Tmax and Cmax) 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. |
| Databáze: | OpenAIRE |
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