DOI: 10.1177/00045632231224215 ISSN: 0004-5632

A rapid, sensitive method for clinical monitoring of Ketamine and Norketamine by UPLC-MSMS

Nicholas Alexei Eric Armfield, Bernhard Frank, Carrie Chadwick
  • Clinical Biochemistry
  • General Medicine

Abstract Background: Ketamine is an NMDAR antagonist with aggregating use across many areas of medicine. P450 enzymes heavily metabolise ketamine where norketamine is a first pass formed metabolite following initial N-demethylation [1]. Serum ketamine monitoring is becoming increasingly important where a sensitive method is required with a robust lower limit of quantitation. Methods: Samples were prepared using protein precipitation or solid phase extraction. Ion suppression was investigated to assess sample preparation technique, followed by reverse phase chromatography coupled with tandem mass spectrometry to analyse extractions using a Waters Xevo TQ-s and associated Acquity chromatography systems. Performance characteristics were analysed to validate the assay. Results: Ketamine and norketamine retention times were 1.28 and 1.23 minutes respectively. Ketamine and norketamine precursor ions fragmented into 2 distinguishable product ions (238.14 > 207.18/125.06 and 224.1 > 178.96/124.86). Performance characteristics highlights include an assay recovery of 103.7% (ketamine) and 96.3% (norketamine), lower limit of quantitation 36.2µg/L (ketamine) and 38.9µg/L (norketamine), and intra-assay imprecision ≤7.04% on average. Conclusions: A robust and reproducible assay with limited sample preparation has been designed and validated. The linearity of the assay covers all ranges of interest reported in the literature. Ion suppression was clearly reduced via use of solid phase extraction. The method will form the basis of ketamine monitoring and providing valuable patient information on tolerance and metabolism.

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