title: Quantification of trantinterol, its two metabolites and their primary conjugated metabolites in human plasma by ultra-high-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.
abstract: A highly rapid, selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to simultaneously determine trantinterol, its major phase-I metabolites and their primary conjugated metabolites in human plasma. Waters Oasis HLB C18 solid phase extraction cartridges were used in the sample preparation. The separation was carried out on an ACQUITY UPLC™ BEH C18 column with methanol/0.2% formic acid (30:70, v/v) as the mobile phase at a flow rate of 0.25 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in selective reaction monitoring (SRM) mode with the use of an electrospray ionization (ESI) source. The linear calibration curves for trantinterol, tert-butyl hydroxylated trantinterol (tert-OH-trantinterol) and 1-carbonyl trantinterol (trantinterol-COOH) were obtained in the concentration ranges of 0.200-250, 0.108-4.00 and 0.0840-5.02 ng/mL, respectively (r(2)≥0.99). The intra- and inter-day precision (relative standard deviation, RSD) values were less than 13%, and the accuracy (relative error, RE) was within ±9.9%, as determined from quality control (QC) samples for the analytes. The concentrations of conjugated forms of trantinterol and tert-OH- trantinterol in plasma were determined using selective enzyme hydrolysis. The method described herein was fully validated and successfully applied for the pharmacokinetic study of trantinterol in healthy volunteers after oral administration.
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qin
authors.affiliation: College of Medical Informatics, China Medical University, Shenyang 110013, PR China.
authors.forename: Bincan
authors.initials: B
authors.lastname: Yin
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Kunjie
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors.forename: Famei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: bearry200@126.com.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xiong
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D002976:Clenbuterol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C542064:trantinterol; D002976:Clenbuterol
keywords: Human plasma; Metabolites; Pharmacokinetics; Trantinterol; UHPLC-MS/MS