title: Quantitative determination of beta,beta-dimethylacrylshikonin (DASK) in rat whole blood by liquid chromatography-tandem mass spectrometry with pre-column derivation and its pharmacokinetic application.
abstract: A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of beta,beta-dimethylacrylshikonin (DASK) in rat whole blood. DASK was pretreated using pre-column derivatization with 2-mercaptoethanol followed by liquid-liquid extraction with cyclohexane. Detection was performed on Thermo Finnigan TSQ Quantum triple quadrupole mass spectrometer by selected reaction monitoring mode via electrospray ionization source. The linear range for the determination of DASK spiked in rat whole blood (0.25 mL) was 3-3000 ng/mL. The accuracy was within 9%. Intra- and inter-day precisions were no more than 16.1 and 13.3%, respectively. The validated LC-MS/MS method was successfully applied to the preliminary pharmacokinetic study in rats. After DASK administration (60 mg/kg, p.o.) in rats, pharmacokinetic parameters were obtained, where the area under the drug concentration-time curve was 2393.7 +/- 224.4 ng h/mL and the elimination half-life was 27.6 +/- 5.3 h.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing 100850, People's Republic of China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Tian
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Sun
authors.forename: Guifang
authors.initials: G
authors.lastname: Dou
authors.forename: Dan
authors.initials: D
authors.lastname: Yuan
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Meng
mesh_terms: D053000:Analytic Sample Preparation Methods; D000818:Animals; D002227:Carbazoles / Q000097:blood / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D009285:Naphthoquinones / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D011422:Propionates / Q000097:blood / Q000737:chemistry; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002227:Carbazoles; D009285:Naphthoquinones; D011422:Propionates; C515629:chiglitazar; C032573:beta, beta-dimethylacrylshikonin