High-throughput pharmacokinetic method: Cassette dosing in mice associated with minuscule serial bleedings and LC/MS/MS analysis

Takaho Watanabe, Daniela Schulz, Christophe Morisseau, Bruce D. Hammock

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

A method for pharmacokinetic studies using cassette dosing associated with serial bleeding in mice is described. PK profiles of four soluble epoxide hydrolase inhibitors were determined following oral, subcutaneous or intraperitoneal administration individually or in cassette dosing. Parent analyses were performed on only 5 μL of whole blood from serial bleeds (up to 10 per animal), by LC/MS/MS. An accuracy (88-100%) and precision (<10% RSD) were observed, leading to reliable datum points for PK calculation. PK profiles, Tmax, Cmax and half-life values after cassette dosing were similar to the individual PK results. This method dramatically increases speed of data collection while dramatically reducing cost and animal usage. The results presented here clearly indicate that this proposed method could be applicable to high-throughput PK studies.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalAnalytica Chimica Acta
Volume559
Issue number1
DOIs
StatePublished - Feb 10 2006

Keywords

  • Cassette dosing
  • High-throughput
  • LC/MS/MS
  • Pharmacokinetics
  • Serial bleeding

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry
  • Spectroscopy
  • Environmental Chemistry

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