Conventional liquid chromatography/triple quadrupole mass spectrometry based metabolite identification and semi-quantitative estimation approach in the investigation of in vitro dabigatran etexilate metabolism

摘要: Dabigatran etexilate (DABE) is an oral prodrug that rapidly converted by esterases to dabigatran (DAB), a direct inhibitor of thrombin. To elucidate the esterase-mediated metabolic pathway DABE, high-performance liquid chromatography/mass spectrometry based metabolite identification and semi-quantitative estimation approach was developed. overcome poor full-scan sensitivity conventional triple quadrupole mass spectrometry, precursor-product ion pairs were predicted search for potential in vitro metabolites. The detected metabolites confirmed product scan. A dilution method introduced evaluate matrix effects on tentatively identified without chemical standards. Quantitative information obtained using "metabolite standards" generated from incubation samples contain high concentration combination with correction factor response. Two DABE (M1 M2) identified, quantified approach. It noteworthy CES1 converts M1 while CES2 mediates conversion M2. M2 further metabolized DAB CES1, respectively. presented here provides solution bioanalytical need fast CES preclinical samples.