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( R )-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM) is a novel Danshensu (DSS) derivative regarded as a potential new agent for the treatment of myocardial ischemia. A validated high performance liquid chromatography (HPLC) approach with a detection limit of 5 ng/mL was used for pharmacokinetic evaluation of ADTM in rat plasma. The intra- and interday precision in terms of relative standard deviation were &lt;4.98 and 4.84%, respectively, at concentration levels of 0.02, 0.20 and 0.80 µg/mL. ADTM's absolute oral bioavailability value was 30.4% and  t  1/2  was 34.33 ± 11.51 and 29.94 ± 8.19 min after oral and intravenous administration of 20 mg/kg. In addition, the major metabolites both  in vitro  and  in vivo  were 2-hydroxymethy-3,5,6-trimethylpyrazin and DSS. The results indicated that the hydrolysis was the main metabolic pathway of ADTM, and carboxylesterase may play an important role in ADTM's metabolism. The present work provides basic information for ADTM's further preclinical research and DSS's chemical structure modification.

Pharmacokinetic and Metabolic Studies of ADTM: A Novel Danshensu Derivative Confers Cardioprotection by HPLC-UV and LC–MS/MS