title: Liquid chromatography-tandem mass spectrometry determination of baclofen in various biological samples and application to a pharmacokinetic study.
abstract: Baclofen is a structural analogue of γ-aminobutyric acid (GABA) that has been used for the treatment of spasticity since 1977. This study describes a simple and sensitive LC/MS/MS assay for the quantification of baclofen in rat plasma, urine, as well as various tissue samples. The assay utilized a simple protein precipitation and achieved lower limit of quantification (LLOQ) of 0.25ng/mL for rat plasma and brain samples and 2ng/mL for rat urine, liver and kidney samples. The assay was validated to demonstrate the specificity, linearity, recovery, LLOQ, accuracy, precision, and stability by using matrix matched quality control samples. There is no endogenous or exogenous peaks interfering with the analytes and matrix effects were minimized by optimized separation condition. The assay was linear over a concentration range of 0.25-500ng/mL for rat plasma and brain tissue, and 2-5000ng/mL for rat urine, kidney and liver with correlation coefficients >0.999. The mean intra- and inter-day assay accuracies were 94.6-104.6 and 96.0-103.6%, respectively. The mean intra- and inter-day precisions were 5.71 and 5.70%, respectively. The developed assay was successfully applied to a pharmacokinetic study and examined urinary excretion and tissue distribution of baclofen in rats following intravenous and oral administration.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Soyoung
authors.initials: S
authors.lastname: Shin
authors.forename: Jeong Cheol
authors.initials: JC
authors.lastname: Shin
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Seo
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Park
authors.forename: Dong Rak
authors.initials: DR
authors.lastname: Kwon
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
authors.forename: Ah-Ram
authors.initials: AR
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Joo
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Min
authors.forename: Won Young
authors.initials: WY
authors.lastname: Yoo
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
mesh_terms: D000818:Animals; D001418:Baclofen / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D016018:Least-Squares Analysis; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D001418:Baclofen
keywords: Baclofen; LC/MS/MS; Pharmacokinetics; Tissue distribution