Development of a novel enantioselective high-performance liquid chromatography-mass spectrometry method for the differentiation of dextro- and levo-methorphan and their O-demethylated metabolites in human blood and its application to post-mortem samples.

Recently we proposed an isocratic enantioselective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the separation and quantitative determination of dextro- (DXM) and levo-methorphan (LVM) and their pharmacologically relevant metabolites, dextrorphan and levorphanol, respectively, in human blood samples. This method was based on the polysaccharide-based chiral column Lux AMP, a specialty column characterized with high stability in mobile phases of pH 11.0 and above. The use of a single-source column is a limitation for any analytical method. Therefore, the major goal of the present study was to develop an enantioselective method for the differentiation of dextro- and levo-methorphan, as well as their metabolites dextrorphan and levorphanol, using Lux Cellulose-3 as alternative chiral column with methanol containing 0.1 % diethylamine mobile phase. A newly developed method uses a chiral selector part of HPLC columns available from multiple manufacturers and a fairly common mobile phase. The method was validated and applied to post-mortem blood samples. Out of 50 analyzed new samples, dextromethorphan (DXM) was detected in 17 samples. Of these 17 cases DXM was accompanied with LVM in 7 samples. The proposed analytical method is relatively simple, accurate and fast and can be adopted for routine use in forensic and clinical toxicology laboratories. Copyright © 2023. Published by Elsevier B.V.

Citation

Saba Jorbenadze, Tamar Khatiashvili, Aluda Chelidze, Alfredo Fabrizio Lo Faro, Tivadar Farkas, Anastasio Tini, Giorgia Sprega, Diletta Berardinelli, Francesco Paolo Busardò, Bezhan Chankvetadze. Development of a novel enantioselective high-performance liquid chromatography-mass spectrometry method for the differentiation of dextro- and levo-methorphan and their O-demethylated metabolites in human blood and its application to post-mortem samples. Journal of pharmaceutical and biomedical analysis. 2024 Jan 05;237:115769

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PMID: 37864951

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