title: A sensitive LC-MS/MS method for simultaneous determination of R-bambuterol and its active metabolite R-terbutaline in human plasma and urine with application to a clinical pharmacokinetic study.
abstract: A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of R-bambuterol and its active metabolite R-terbutaline in human plasma and urine was established. The inhibition for the biotransformation of R-bambuterol in plasma was fully investigated. Plasma samples were prepared on ice and neostigmine metilsulfate added as a cholinesterase inhibitor immediately after sample collection. All samples were extracted with ethyl acetate and separated on a C₁₈ column under gradient elution with a mobile phase consisting of methanol and water containing 5 mm ammonium acetate at a flow rate of 0.6 mL/min. The analytes were detected by an API 4000 tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 10.00 pg/mL for each analyte in plasma. In urine samples, the LLOQs were 20.00 and 500.0 pg/mL for R-bambuterol and R-terbutaline, respectively. The intra- and inter-day precisions were <12.7 and <8.6% for plasma and urine, respectively. The analytical runtime within 6.0 min per sample made this method suitable for high-throughput determination. The validated method has been successfully applied to the human pharmacokinetic study of R-bambuterol involving 10 healthy volunteers.
authors.affiliation: School of Bioscience and Bioengineer, South China University of Technology, Guangzhou, Guangdong, 510006, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.forename: Qing
authors.initials: Q
authors.lastname: Cheng
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
mesh_terms: D000284:Administration, Oral; D001711:Biotransformation; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013726:Terbutaline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*
chemical_list: D013726:Terbutaline; C047766:bambuterol
keywords: LC-MS/MS; R-bambuterol; R-terbutaline; pharmacokinetics