title: Determination of dihydromyricetin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.
abstract: Ampelopsis grossedentata (Hand.-Mazz.) W.T. Wang has long been used as a traditional Chinese medicinal herb among the indigenous people in the Yangtze River region of China. Dihydromyricetin (DMY) is the most abundant (approximately 30%) and bioactive constituent in A. grossedentata (Hand.-Mazz.) W.T. Wang, and recent studies have demonstrated its various pharmacological activities. In the present study, a first specific, sensitive, rapid and reliable LC-MS/MS method for the determination of DMY in rat plasma was developed and validated. The plasma samples were prepared with protein precipitation method, and chromatographic separation was performed on a Welch Ultimate XB-C18 column (50 × 2.1 mm, 5 μm) using a gradient elution with water and acetonitrile. The mass spectrometry (MS) analysis was conducted in negative ionization mode with multiple reaction monitoring (MRM) transitions at m/z 319.1→192.8 for DMY and m/z 609.0→301.2 for rutin (IS). The plasma concentration profiles and pharmacokinetic parameters were analyzed after oral administration of dextroisomer and racemate DMY at the dose of 100 mg/kg in rats. The method validation was conducted over the calibration range of 10.0-5000 ng/ml with the intra- and inter-day precision and accuracy within 12.0% (RSD) and 5.6% (RE). The recoveries, matrix effect and stability under different conditions were all proved acceptable. The values of Tmax, AUC(0-∞) and Vd were significantly different between the groups of dextroisomer and racemate DMY (P<0.05), and pharmacokinetic results revealed their poor absorptions into blood, probably high tissue distributions and slow elimination processes. The present study will provide helpful information for the further studies and future clinical applications of DMY.
authors.affiliation: Department of Pharmacy, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Department of Pharmacy, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Pharmacy, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Pharmacy, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Pharmacy, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xuejia
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: shichunyang_tj@163.com.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Shi
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000032:analysis; D005260:Female; D044948:Flavonols / Q000097:blood* / Q000493:pharmacokinetics; D006461:Hemolysis; D008297:Male; D013058:Mass Spectrometry; D010100:Oxygen / Q000737:chemistry; D010949:Plasma / Q000378:metabolism; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D000097:Acetonitriles; D004365:Drugs, Chinese Herbal; D044948:Flavonols; D014867:Water; C472036:dihydromyricetin; D010100:Oxygen; C032159:acetonitrile
keywords: Ampelopsis grossedentata; Dihydromyricetin; LC–MS/MS; Pharmacokinetic; Rat plasma