Metabolism and bioactivation of the tricyclic antidepressant amitriptyline in human liver microsomes and human urine.
AIM Amitriptyline is a widely used tricyclic antidepressant, but the metabolic studies were conducted almost 20 years ago using high performance liquid chromatography coupled with ultraviolet detector or radiolabeled methods. RESULTS First, multiple ion monitoring (MIM) enhanced product ion (EPI) scan was used to obtain the diagnostic ions or neutral losses in human liver microsome incubations with amitriptyline. Subsequently, predicted multiple reaction monitoring (MRM) EPI scan was used to identify the metabolites in human urine with the diagnostic ions or neutral losses. Finally, product ion filtering and neutral loss filtering were used as the data mining tools to screen metabolites. Consequently, a total of 28 metabolites were identified in human urine after an oral administration using LC MS/MS. CONCLUSION An integrated workflow using LC MS/MS was developed to comprehensively profile the metabolites of amitriptyline in human urine, in which five N acetyl l cysteine conjugates were characterized as tentative biomarkers for idiosyncratic toxicity.
Bioanalysis