title: Application of an LC-MS/MS method to the pharmacokinetics of TM-2, a potential antitumour agent, in rats.
abstract: TM-2 is a novel semi-synthetic taxane derivative, selected for preclinical development based on its greater anticancer activity and lower toxicity compared with docetaxel. In this study, a rapid and sensitive analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of TM-2 in rat plasma. The biological samples were extracted with methyl tert-butyl ether and separated on a C18 column (50 mm × 2.1 mm, 1.7 µm) using a mobile phase consisting of acetonitrile and 2 mM ammonium acetate. The standard curves were linear over the range 5-1000 ng/mL in rat plasma. The precision (relative standard deviation, RSD, %) were within 14.5%, and the accuracy (relative error, RE, %) ranged from -1.56 to 2.36%. Recovery and matrix effect were satisfactory in rat plasma. The validated method was successfully applied to pharmacokinetic studies after intravenous administration of TM-2 to rats. The pharmacokinetics of TM-2 in rats were characterized by a large volume of distribution and a long half-life of elimination after single dose (4, 8, and 16 mg/kg), and a good correlation was observed between AUC and dose. The preclinical data will be useful for the design of subsequent trials of TM-2.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Men
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Lin
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Shao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051381:Rats; D053719:Tandem Mass Spectrometry; D043823:Taxoids / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: C000593048:13-(N-tert-butoxycarbonyl-3-isobutylisoserinoyl-4,10-diacetoxy-2-benzoyloxy-5-20-epoxy-1,13-dihydroxy-9-oxo-19-norcyclopropa(g)tax-11-ene; D000970:Antineoplastic Agents; D043823:Taxoids
keywords: LC-MS/MS; a novel taxane derivative; antitumour; pharmacokinetics