Determination of 2-fluoro-deschloroketamine and Its Metabolites in Urine by HPLC-MS/MS

In this paper, the specific structures of two first-phase metabolites of 2-fluoro-deschloroketamine except nor-2-fluoro-deschloroketamine were determined, and a detection method of 2-fluoro-deschloroketamine, nor-2-fluoro- deschloroketamine, cis-Dihydro-2-fluoro-deschloroketamine and trans-Dihydro-2-fluoro-deschloroketamine in urine was estabished using HPLC-QQQ MS/MS. Through HPLC-HRMS screening, two metabolites of 2-fluoro-deschloroketamine, namely cis-Dihydro-2- fluoro-deschloroketamine and trans-Dihydro-2-fluoro-deschloroketamine were determined and then were synthesized specifically. The structures were identified by 1H NMR, 13C NMR and 2D NOE NMR. The HPLC-QQQ MS/MS method for the detection of 2-fluoro-deschloroketamine, nor-2-fluoro-deschloroketamine, cis-Dihydro-2-fluoro- deschloroketamine and trans-Dihydro-2-fluoro-deschloroketamine in urine was established, which possesses a good linear relationship for 2-fluoro-deschloroketamine and its three main metabolites at the concentration range of 0.5~200 ng/mL, with the linear correlation coefficients all greater than 0.996 3, and the recoveries ranging from 81.60% to 119.33%. The quantitation of 2-fluoro-deschloroketamine and its three metabolites in actual urine samples was detected by the established method. This study determined the specific structures of two first-phase metabolites of 2-fluoro-deschloroketamine. The developed testing method has low detection limit, high recovery, and good reproducibility, which can be used in the qualitative and quantitative detection for the stable metabolites of 2-fluoro-deschloroketamine.