Determination of S-(-)-Cathinone and Its Main Metabolite R,S-(-)-Norephedrine In Human Plasma By High-Performance Liquid Chromatography and Photodiode Array Detection

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Abstract
A HPLC procedure is described that uses photodiode array detection (DAD) for the determination of S-(-)-cathinone and of its main metabolite R,S-(-)-norephedrine in human plasma. After addition of (±)-amphetamine as internal standard, extraction and clean-up are done on a cyano-bonded solid-phase column with water and methanol-phosphate buffer as mobile phases. HPLC analysis of plasma extracts is performed on a 3-μm ODS column with acetoni-found very sensitive to matrix interferences and overloading and thus inadequate for the analysis of plasma samples. Even by changing the mobile phase the enantiomers of NE and NPE could not be resolved. Instead, the determination of CA and NE isomers was performed by GC/MS after on-column derivatization with chiral TPC to the corresponding diastereomers. By comparing with pure standards it could be shown that CA in plasma has S configuration (CA-TPC: m/z 237, 194, 166, 105; tR 7.10 min) and that the main metabolite of CA is the R,S configurated (-)-norephedrine (NE-TPC: m/z 238, 237, 194, 166, 139; tR 7.14 min). the TPC derivatives of R-(+)-cathinone (tR 6.62 min), S,R-(+)-norephedrine (tR 6.87 min), S,S-(+)-norpseudoephedrine (tR 7.21 min) and R,R-(-)-norpseudoephedrine (tR 6.96 min) were not found in the plasma samples. This confirms our earlier postulate (8) that CA is mainly metabolized by a stereospecific R keto reduction to the R,S configurated (-)-aminoalcohol (Fig. 1). the absence of R-(+)-cathinone and the corresponding metabolite R,R-(-)-norpseudoephedrine shows that during absorption and distribution in the human body, CA is not racemized, or at least not to a detectable degree.