title: Simultaneous determination of leucine, isoleucine and valine in Beagle dog plasma by HPLC-MS/MS and its application to a pharmacokinetic study.
abstract: Leucine (Leu), isoleucine (Ile) and valine (Val) are three branched-chain amino acids (BCAAs), which have been widely used as dietary supplements for professional athletes and patients with liver failure or catabolic diseases. To date, no pharmacokinetic studies of BCAAs in vivo useful for the assessment of clinical effect following daily intake has been reported. Thus in this study, an HPLC-MS/MS method for simultaneous determination of Leu, Ile and Val in Beagle dog plasma using homoarginine as the internal standard was developed and validated in terms of specificity, linearity, precision, accuracy, and stability. This assay method was then applied to a pharmacokinetic study of BCAAs in dogs following oral administration of 0.25 g/kg and 0.50 g/kg BCAAs. The HPLC-MS/MS method was found to be sensitive and reproducible for quantification of BCAAs in dog plasma and successfully applied to the pharmacokinetic study. All these BCAAs were well absorbed with a substantial increase in the plasma concentration after a baseline modification. No statistical significance was identified in different gender group and no drug accumulation was observed following multiple doses.
authors.affiliation: Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug Ministry of Education, West China School of Pharmacy, Sichuan University, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug Ministry of Education, West China School of Pharmacy, Sichuan University, China.
authors.forename: Huiru
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug Ministry of Education, West China School of Pharmacy, Sichuan University, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug Ministry of Education, West China School of Pharmacy, Sichuan University, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug Ministry of Education, West China School of Pharmacy, Sichuan University, China. Electronic address: rebeccawang312@gmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D005260:Female; D007532:Isoleucine / Q000097:blood / Q000493:pharmacokinetics*; D007930:Leucine / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010949:Plasma / Q000737:chemistry*; D011786:Quality Control; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014633:Valine / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D007532:Isoleucine; D007930:Leucine; D014633:Valine
keywords: BCAAs; Beagle dog plasma; Gender; HPLC–MS/MS; Pharmacokinetics