Objective To study the pharmacokinetics and detection window of clozapine and its metabolites in human blood, so as to provide experimental basis for forensic cases of identification of clozapine poisoning. Methods 29 Taiyuan Han people's elbow venous blood was collected after given oral administration of 12.5mg clozapine at different time point, in which clozapine and its metabolites were extracted with solid phase extraction (SPE) and determined by HPLC-MS-MS. The qualitative analysis was based on retention time and MRM ions. The quantitative analysis was based on an internal standard method and calibration curve. Using the 3p97 pharmacokinetic software, pharmacokinetic equation of clozapine in the blood were imitated from the C-T data, and pharmacokinetic parameters were calculated. Results The pharmacokinetics of clozapine met a two compartment open model with a first kinetics absorption. The Tmax of clozapine(CLP), demethylclozapine(DMCLP), N-oxidation-clozapine(NO-CLP) respectively were 2.96±1.32h, 8.65±3.00h, 9.31±26.38h; The Cmax of CLP, DMCLP, NO-CLP respectively were 34.68±9.32ng/mL, 11.16±4.15ng/mL, 9.62±13.88ng/mL;The t1/2 of CLP, DMCLP, NO-CLP respectively were 17.02±23.63h, 27.06±12.58h, 41.27±29.75h; The detection window of CLP, DMCLP, NO-CLP respectively were 81.72±26.19h, 93.21±29.40h and 19.93±14.62h. Conclusion The pharmacokinetics of clozapine in blood of Han people is consistent with two compartment open model with a first kinetics absorption. The pharmacokinetics model and parameters of clozapine can provide expirimental basis for forensic identification of clozapine poisoning cases.

In this study, the effects and mechanisms of miR-23b in the AD cell model were explored. Aβ25-35 was used to induce neuronal injury model, and cell viabilities were detected by MTT assay. The effect of miR-23b on the apoptotic levels of Aβ25-35-induced SH-SY5Y cells was analyzed using Annexin V-FITC/PI detection kit. The effect of miR-23b on the mitochondrial membrane potential of Aβ25-35-induced SH-SY5Y cells was examined using JC-1 fluorescent probe. The levels of cell apoptosis-related proteins and autophagy-related proteins were detected by Western blot. The results showed that miR-23b could alleviate the apoptosis and the abnormal mitochondrial membrane potential in SH-SY5Y cells induced by Aβ25-35.This study suggested that miR-23b may attenuate Aβ25-35-induced neuronal apoptosis by regulating apoptosis and autophagy-related pathway.