Objective To investigate the in vitro metabolites and metabolic pathways of phenethylamine new psychoactive substances 2C-B-FLY and 25B-NBOH in human liver microsomes.Methods The human liver microsome incubation model was established,and the samples were centrifuged,blow-dried and re-dissolved after 3 h of co-incubation in a water bath at 37℃.The samples were detected by ultra-high performance liquid chromatography Q Exactive mass spectrometry in ESI+mode,and the parent drug and its metabolites were examined by applying Full scan-ddMS2 data-dependent acquisition mode.Results After in vitro incubation with human liver microsomes,2C-B-FLY was metabolised to produce a total of four phase I metabolites and one acetylated phase II metabolite,which underwent metabolic reactions such as hydroxylation,debromination,and N-acetylation.25B-NBOH was metabolised to produce a total of eight phase I metabolites and two glucuronidated phase II metabolites,which comprised the major biotransformation reactions of O-demethylation,hydroxylation,amine dehydrogenation,N-dealkylation and glucuronidation.Conclusion This study describes the metabolites and metabolic pathways of 2C-B-FLY and 25B-NBOH in a human liver microsomal incubation system,providing a scientific basis for the in vivo detection of new psychoactive substance of the phenethylamine group.

Objective To evaluate the value of intrathecal synthetic related markers in patients with mild cognitive impairment(MCI),Alzheimer's disease(AD),and other types of dementia.Methods Retrospec-tively collect the clinical data of 577 patients diagnosed with MCI(MCI group,178 cases),AD(AD group,131 cases),and other types of dementia(other types group,268 cases)from June 2019 to July 2023 in Beijing Tiantan Hospital,Capital Medical University.Oligoclonal zone electrophoresis(OCB)and 24 h intrathecal pro-tein synthesis rate(ISR)of each group were investigated,and the difference of different indexes among the groups was compared to evaluate the value of related indexes in the differential diagnosis of different diseases.Results Compared with AD group and other groups,AD group had a higher proportion of females,more patients were＞50-70 years old,and the incidence of abnormal lipid metabolism was higher,with statistical significance(P＜0.05).There were significant differences in OB(S),cerebrospinal fluid albumin,serum albumin and cerebrospinal flu-id IgG in different disease groups(P＜0.05).IgG index and ISR in patients with positive SOB(CSF)were higher than those in negative and weakly positive patients,and the differences were statistically significant(P＜0.001).IgG index was positively correlated with ISR(r=0.878,P＜0.001).Conclusion Intrathecal synthetic mark-ers such as IgG index,SOB(CSF)and 24 h ISR have synergistic effects in the diagnosis of cognitive dysfunction and various dementias,which can be collectively utilized in the diagnosis of diseases.