title: Pharmacokinetic and Metabolic Studies of ADTM: A Novel Danshensu Derivative Confers Cardioprotection by HPLC-UV and LC-MS/MS.
abstract: (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 <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 t1/2 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.
authors.affiliation: Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China Traditional Chinese Medicine Integrated Hospital of Southern Medical University, Guangzhou 510315, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Luchen
authors.initials: L
authors.lastname: Shan
authors.affiliation: Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Kaiyi
authors.initials: K
authors.lastname: Liao
authors.affiliation: Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Traditional Chinese Medicine Integrated Hospital of Southern Medical University, Guangzhou 510315, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China pennypeiyu@163.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.affiliation: Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D007773:Lactates; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D010666:Phenylpropionates / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D011719:Pyrazines / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C000596359:(3,5,6-trimethylpyrazinyl)methyl 2-acetoxy-3-(3,4-diacetoxyphenyl)propanoate; D002316:Cardiotonic Agents; D007773:Lactates; D010666:Phenylpropionates; D011719:Pyrazines; C035055:3,4-dihydroxyphenyllactic acid