A rapid, sensitive method for clinical monitoring of ketamine and norketamine by ultra-high-performance reverse-phase liquid chromatography tandem mass spectrometry

被引:1
作者
Armfield, Nicholas [1 ,4 ]
Frank, Bernhard [2 ,3 ]
Chadwick, Carrie [1 ]
机构
[1] Walton Ctr NHS Fdn Trust, Neurosci Labs, Liverpool, England
[2] Walton Ctr NHS Fdn Trust, Pain Med, Liverpool, England
[3] Univ Liverpool, Pain Res Inst, Liverpool, England
[4] Walton Ctr NHS Fdn Trust, Neurosci Labs, Lower Ln, Liverpool L9 7LJ, England
关键词
Ketamine; therapeutic drug monitoring; liquid chromatography tandem mass spectrometry; method development; PLASMA; METABOLITES; MS/MS;
D O I
10.1177/00045632231224215
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
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. Serum ketamine monitoring is becoming increasingly important, requiring a sensitive method with a robust lower limit of quantitation.Methods: Samples were prepared using protein precipitation or solid phase extraction. Ion suppression was investigated to optimise sample preparation technique, followed by reverse-phase chromatography coupled with tandem mass spectrometry to analyse extractions using a Waters Xevo TQ-S Micro 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 min, 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 include an assay recovery of 103.7% (ketamine) and 96.3% (norketamine), lower limit of quantitation 36.2 mu g/L (ketamine) and 38.9 mu g/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.
引用
收藏
页码:309 / 318
页数:10
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