title: Simultaneous quantification of tafetinib (SIM010603), a novel potent inhibitor of receptor tyrosine kinase, and its major metabolite in dog plasma by HPLC-ESI/MS/MS and its application to a pharmacokinetic study.
abstract: This study presents a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI/MS/MS) technique for the simultaneous determination of tafetinib (SIM010603) and its main metabolite (M1) in dog plasma by using Prazosin hydrochloric acid as the internal standard (IS). Both compounds were extracted from dog plasma with ethyl acetate and were separated by HPLC on a reversed phase C₁₈ column with a mobile phase of 10 mM ammonium acetate buffer containing 0.1% formic acid-acetonitrile (40:60, v/v) at a flow rate of 0.2 mL/min. For quantification, the triple-quadruple MS was used in selected reaction monitoring (SRM) mode. The monitored transitions were m/z 425.3 → 309.2 for tafetinib, m/z 397.2 → 309.2 for M1 and m/z 384.2 → 247.1 for IS. The developed method had a short run time of 4 min and good linearity was observed over a wide range of 1-1000 ng/mL for the two compounds. The method was successfully applied in the pharmacokinetic study of tafetinib and M1 in dog.
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Jiangsu Simcere Pharmaceutical R&D Co. Ltd., Nanjing 210042, PR China. shaofeng33@yahoo.com
authors.forename: Feng
authors.initials: F
authors.lastname: Shao
authors.forename: Tian
authors.initials: T
authors.lastname: Zhu
authors.forename: Feng
authors.initials: F
authors.lastname: Tang
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods; D004285:Dogs; D005021:Ethylamines / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D007211:Indoles / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D011224:Prazosin / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
chemical_list: D005021:Ethylamines; D007211:Indoles; C570037:N-(2-(diethylamino)ethyl)-2-methyl-7-(1,2-dihydro-5-fluoro-2-oxo-3H-indol-3-ylidene)-4,5,6,7-tetrahydro-1H-indole-3-carboxamide; D047428:Protein Kinase Inhibitors; D011224:Prazosin