title: Determination of tulobuterol in rat plasma using a liquid chromatography-tandem mass spectrometry method and its application to a pharmacokinetic study of tulobuterol patch.
abstract: A sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for determination of tulobuterol in rat plasma for the first time. Plasma samples were extracted by liquid-liquid extraction method with methyl tert-butyl ether and the analyte and clenbuterol (IS) were separated on a Venusil MP C18 column (100mm×2.1mm, 3μm) using 0.1% formic acid-water-methanol as mobile phase, with a runtime of 5min. The analyte was detected in multiple reaction monitoring (MRM) mode with positive electrospray ionization. Transitions of m/z 228.2→154.0 for tulobuterol and m/z 277.1→203.0 for the clenbuterol were monitored. The linear range was 0.5-100ng/ml (r=0.9967) for tulobuterol with the lower limit of quantitation of 0.5ng/ml. The intra-day and inter-day precisions were less than 10.3% for the analyte and the accuracy was less than -8.6%. The RSD of matrix effect and recovery yield were within ±15% of nominal concentrations and tulobuterol was stable during stability studies. The validated method has been successfully applied to a pharmacokinetic study of three doses of tulobuterol patch in rats for the first time.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Ji
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Hui
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China. Electronic address: kaishunbi.syphu@gmail.com.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
mesh_terms: D000318:Adrenergic beta-Agonists / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013726:Terbutaline / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000318:Adrenergic beta-Agonists; C010809:tulobuterol; D013726:Terbutaline
keywords: ESI; HPLC; IS; LC–MS/MS; LLE; LLOQ; Linear pharmacokinetic study; MF; MR; QC; RE; RSD; Transdermal administration; Tulobuterol patch; electrospray ionization; high performance liquid chromatography; internal standard; liquid chromatography–tandem mass spectrometry; liquid–liquid extraction; lower limit of quantification; matrix factor; multiple reaction monitoring; quality control; relative error; relative standard deviation