title: Chiral analysis of bambuterol, its intermediate and active drug in human plasma by liquid chromatography-tandem mass spectrometry: Application to a pharmacokinetic study.
abstract: A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for simultaneous chiral analysis of an antiasthma drug bambuterol, its key intermediate monocarbamate bambuterol and its active drug terbutaline in human plasma. All samples were extracted with ethyl acetate and separated on an Astec Chirobiotic T column under isocratic elution with a mobile phase consisting of methanol and water with the addition of 20mm ammonium acetate and 0.005% (v/v) formic acid at 0.6mL/min. The analytes were detected by a Xevo TQ-S tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method has high sensitivity with the lower limit of quantifications of 25.00pg/mL for bambuterol enantiomers, and 50.00pg/mL for monocarbamate bambuterol and terbutaline enantiomers, respectively. The calibration curves for bambuterol enantiomers were linear in the range of 25.00-2500pg/mL, and for monocarbamate bambuterol and terbutaline enantiomers were linear in the range of 50.00-5000pg/mL. The intra- and inter-day precisions were <12.4%. All the analytes were separated in 18.0min. For the first time, the validated method was successfully applied to an enantioselective pharmacokinetic study of rac-bambuterol in 8 healthy volunteers. According to the results, this chiral LC-MS/MS assay provides a suitable and robust method for the enantioselectivity and interaction study of the prodrug bambuterol, the key intermediate monocarbamate bambuterol and its active drug terbutaline in human.
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-incubtor for Innovative Drug & Medicine, School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-incubtor for Innovative Drug & Medicine, School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-incubtor for Innovative Drug & Medicine, School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-incubtor for Innovative Drug & Medicine, School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: He
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Beining
authors.initials: B
authors.lastname: Xu
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Qu
authors.affiliation: Keypharma Biomedical Inc., Songshan Lake Science & Technology Industry Park, Dongguan 523808, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-incubtor for Innovative Drug & Medicine, School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China. Electronic address: went@scut.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods; D013726:Terbutaline / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D013726:Terbutaline; C047766:bambuterol
keywords: Bambuterol; Chiral analysis; Clinical pharmacokinetics; Intermediate; LC–MS/MS