Detection Of Antipsychotics Based On Three Sensitive Analysis Methods

Drug therapy is the main method for treating mental illnesses.Due to the low safety index of drugs used to treat mental illnesses,monitoring the drug concentration of patients is particularly important.At present,there are shortcomings in the monitoring methods for this type of drug,such as low sensitivity,poor selectivity,and time-consuming.To address this issue,it is necessary to develop a fast,sensitive,and reliable detection method,which is of great significance for drug guidance in the treatment of mental illness.This paper is based on three different analytical methods for the detection of various drugs used to treat mental disorders,and the established methods are validated and analyzed,ultimately applied to the detection of actual samples.The specific content is as follows:Part Ⅰ:The combined abuse of antipsychotics has become a global problem,to develop a highly sensitive and selective method for monitoring of sedative hypnotics and antipsychotics is urgently necessary.In this work,we established a rapid method for the simutaneous determination of antipsychotic drugs(diazepam,alprazolam,triazolam,estazolam,clozapine and chlorpromazine based on ultra performance liquid chromatography-mass spectrometry（UPLC-MS/MS）.The accuracy,precision,limit of detection（LOD）,limit of quantification（LOQ）,specificity,matrix effect and carryover effect were verified in detail.The results of the recovery and repeat experiments proved that the proposed UPLC-MS/MS method possessed very satisfactory accuracy and precision.The LOD and LOQ of the six psychoactive substances were as low as0.001-0.005 and 0.005-0.01μg/L,respectively.The proposed method was employed to analyze the urine sample which was pretreated by protein precipitation process.The potential influences of precipitants on analysis results were evaluated statistically,and0.1%formic acid acetonitrile water was selected as the optimum precipitation agent.The detection of the targets were free from the matrix and carryover effects.Part Ⅱ:In this study,carbon nitride nano-sheets（g-C₃N₄Ns）with blue fluorescence was synthesized by a simple and easy ultrasonic stripping method.The structure,morphology and optical properties of g-C₃N₄Ns were investigated by X-ray photoelectron spectroscopy（XPS）,transmission electron microscopy（TEM）,Fourier transform infrared spectroscopy（FTIR）,fluorescence spectrometer（FL）,and UV-visible spectrophotometer（UV）.CLZ quenches the blue fluorescence of g-C₃N₄Ns in the form of dynamically quenched charge transfer.Under the optimal experimental conditions,a standard curve was established for the correlation between the CLZ concentration and the fluorescence quenching degree of g-C₃N₄Ns.The results showed that the linear relationship was good in the concentration range of 0.02-500.00μM,and LOD could be as low as 3 n M.It has been applied to the detection of bovine serum and clozapine tablet samples,with a recovery rate of 97.2%-104.7%.In addition,when other interfering ions coexist,the interference effect can be ignored,showing good selectivity.In summary,our proposed fluorescence analysis method can achieve rapid,sensitive,selective detection of CLZ and quantitative analysis of actual samples.Part Ⅲ:Electrochemical sensing technology has the advantages of low cost,simple pretreatment,fast response,high sensitivity and high selectivity,etc.,which has been widely concerned in the field of drug and biomolecular detection.Based on graphite-phase carbon nitride nanomaterials,2D palladium/phosphorus co-doped carbon nitride（Pd/P-g-C₃N₄）was prepared by element doping（P element and Pd）to improve the electron transport capacity of the materials.The Pd/P-g-C₃N₄was modified on the surface of a glassy carbon electrode to construct an electrochemical sensor.It is also used for trace detection of dopamine and antipsychotic drugs（clozapine and chlorpromazine）.The results showed that under the optimal experimental conditions,the three analytes had a good linear relationship in the range of subtherapeutic,therapeutic and toxic concentrations,and the detection limit was as low as 5 n M.Even in the presence of other interfering ions,the interference effect is negligible.It was applied to the determination of target substance in drugs and bovine serum samples.The recoveries were in the range of 95.9%-102.0%with satisfactory results.