A critical point in chiral chromatography-mass spectrometry analysis of ketamine metabolites.

Drug Testing and Analysis
Andrea BarbarossaGiampiero Pagliuca

Abstract

Ketamine is a widely used dissociative drug, whose quantification in plasma and urine can be of pharmacological, toxicological, and clinical interest. Although tandem mass spectrometry allows the reliable determination of ketamine and its metabolites in biological matrices, the structural similarity between norketamine (main active metabolite) and dehydronorketamine (a less relevant metabolite) can represent a critical aspect. These compounds differ exclusively in two hydrogen atoms, but the consequent two-unit difference in their mass/charge ratio is partially nullified by the isotopic abundance of the chlorine atom present in their structure. This, along with their similar fragmentation pattern, can result in the incorrect identification of the enantiomers of these ketamine metabolites even with triple quadrupole instruments, if shared transitions are monitored after chiral chromatography. The key to prevent norketamine overestimation is therefore observing analyte-specific MS/MS transitions. Here, we describe in detail how we investigated this issue, during the development of an analytical method for ketamine and norketamine enantiomer determination in plasma.

References

Jul 31, 2003·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Maria Esther Rodriguez RosasIrving W Wainer
Nov 4, 2008·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Mark C ParkinAndrew T Kicman
May 19, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sophie C TurfusAndrew T Kicman
Oct 7, 2009·Analytical and Bioanalytical Chemistry·María Jesús TaberneroMarcello Chiarotti
Oct 9, 2015·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Ivo MorenoEugenia Gallardo
Aug 28, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Adriana S BarretoSilvana V Rodrigues

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