OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

Objective To establish a purification,enrichment and test method of tetrodotoxin in blood.Methods Through the investigation of various hydrophilic chromatographic columns,the comparison of extraction effects of different types of solid phase extraction columns and the interference analysis of mixed peaks on qualitative ion pairs,the matrix influence of tetrodotoxin was reduced,and the detection sensitivity and qualitative accuracy were improved.Results Tetrodotoxin is highly polar and easily inhibited by the matrix,while conventional precipitation protein method has low sensitivity and isomer double peaks,and the C18 column is not reserved.After comprehensive comparative analysis,the weak cation exchange column PWC column is finally used for purification and enrichment.Complete elution was achieved using 0.5 mL 10%formic acid and 50%acetonitrile aqueous solution.Seperation was performed on an Atlantis HILIC column,with qualitative ion pairs set at m/z,320.10>162.15 and 284.15.The detection limit of the method was 0.061 ng/mL.Conclusion The established PWC solid-phase extraction-LC/MS detection method demonstrates significant purification efficacy,minimal matrix influence,unobstructed chromatographic peaks,markedly improved detection sensitivity.This approach is operationally simple,and applicable to forensic casework.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective To establish a purification,enrichment and test method of tetrodotoxin in blood.Methods Through the investigation of various hydrophilic chromatographic columns,the comparison of extraction effects of different types of solid phase extraction columns and the interference analysis of mixed peaks on qualitative ion pairs,the matrix influence of tetrodotoxin was reduced,and the detection sensitivity and qualitative accuracy were improved.Results Tetrodotoxin is highly polar and easily inhibited by the matrix,while conventional precipitation protein method has low sensitivity and isomer double peaks,and the C18 column is not reserved.After comprehensive comparative analysis,the weak cation exchange column PWC column is finally used for purification and enrichment.Complete elution was achieved using 0.5 mL 10%formic acid and 50%acetonitrile aqueous solution.Seperation was performed on an Atlantis HILIC column,with qualitative ion pairs set at m/z,320.10>162.15 and 284.15.The detection limit of the method was 0.061 ng/mL.Conclusion The established PWC solid-phase extraction-LC/MS detection method demonstrates significant purification efficacy,minimal matrix influence,unobstructed chromatographic peaks,markedly improved detection sensitivity.This approach is operationally simple,and applicable to forensic casework.

BACKGROUND:Metabonomics has been proved to analyze and observe the pathological process of rat myocardial infarction and the underlying mechanism. OBJECTIVE:To further analyze the metabolomic pathways of bioinformatics in rat models of myocardial infarction. METHODS:The experimental studies about rat myocardial infarction were retrieved from CNKI, WanFang, CqVip, PubMed and Embase databases. The metabolic products described in the literatures were col ected and summarized. Signaling pathways were analyzed using KEGG database molecular function annotation, the enzymes, translocators and their properties were analyzed by HMDB database. Metabolites pathway were visualized with MetPA. RESULTS AND CONSLUSION:A total of 26 metabolic products were identified in the included literatures and mainly participated in 29 metabolic pathways. Through topology analysis, 5 of the 10 metabolic pathways were selected and regarded as the metabolic pathways of myocardial infarction in rats, including aminoacyl-tRNA biosynthesis;glycine, serine and threonine metabolism;valine, leucine and isoleucine biosynthesis;biosynthesis of unsaturated fatty acids;phenylalanine, tyrosine and tryptophan biosynthesis. In conclusion, the bioinformatics analysis of metabolites in rats with myocardial infarction show that myocardial infarction is related to the metabolism and metabolic pathways of carbohydrates, proteins, fat and RNA.