Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 54, Issue 27, Pages 7815-7818Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201503312
Keywords
breath analysis; high-resolution mass spectrometry; ketamine; pharmacokinetics; secondary electrospray ionization
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Funding
- Marie Curie European Reintegration Grant within the European Community [276860]
- Zurich Clinical Research Priority Program Sleep and Health
- Swiss Cancer League
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Noninvasive, real-time pharmacokinetic (PK) monitoring of ketamine, propofol, and valproic acid, and their metabolites was achieved in mice, using secondary electrospray ionization and high-resolution mass spectrometry. The PK profile of a drug influences its efficacy and toxicity because it determines exposure time and levels. The antidepressant and anaesthetic ketamine (Ket) and four Ket metabolites were studied in detail and their PK was simultaneously determined following application of different sub-anaesthetic doses of Ket. Bioavailability after oral administration vs. intraperitoneal injection was also investigated. In contrast to conventional studies that require many animals to be sacrificed even for low-resolution PK curves, this novel approach yields real-time PK curves with a hitherto unmatched time resolution (10s), and none of the animals has to be sacrificed. This thus represents a major step forward not only in animal welfare, but also major cost and time savings.
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