Enantioselective CE–MS analysis of ketamine metabolites in urine. Issue 1 (9th December 2022)

• Record Type: Journal Article
• Authors: Sandbaumhüter, Friederike A.; Aerts, Jordan T.; Theurillat, Regula; Andrén, Per E.; Thormann, Wolfgang; Jansson, Erik T.
• Other Names: Lapizco‐Encinas Blanca guestEditor.; Wätzig Hermann guestEditor.
• Is Part Of: Electrophoresis. Volume 44:Issue 1/2(2023)
• Page Start: 125
• Page End: 134
• Publication Date: 2022-12-09
• Subjects: capillary electrophoresis–mass spectrometry -- chiral separation -- hydroxynorketamine -- ketamine -- partial filling; Electrophoresis -- Periodicals; Electrophoresis -- Periodicals; 541.372
• DOI: 10.1002/elps.202200175
• Languages: English
• ISSNs: 0173-0835

Abstract

Abstract: The chiral drug ketamine has long‐lasting antidepressant effects with a fast onset and is also suitable to treat patients with therapy‐resistant depression. The metabolite hydroxynorketamine (HNK) plays an important role in the antidepressant mechanism of action. Hydroxylation at the cyclohexanone ring occurs at positions 4, 5, and 6 and produces a total of 12 stereoisomers. Among those, the four 6HNK stereoisomers have the strongest antidepressant effects. Capillary electrophoresis with highly sulfated γ‐cyclodextrin (CD) as a chiral selector in combination with mass spectrometry (MS) was used to develop a method for the enantioselective analysis of HNK stereoisomers with a special focus on the 6HNK stereoisomers. The partial filling approach was applied in order to avoid contamination of the MS with the chiral selector. Concentration of the chiral selector and the length of the separation zone were optimized. With 5% highly sulfated γ‐CD in 20 mM ammonium formate with 10% formic acid and a 75% filling the four 6HNK stereoisomers could be separated with a resolution between 0.79 and 3.17. The method was applied to analyze fractionated equine urine collected after a ketamine infusion and to screen the fractions as well as unfractionated urine for the parent drug ketamine and other metabolites, including norketamine and dehydronorketamine.