title: Quantification of henatinib maleate, a novel potent inhibitor of VEGF receptors, in rat plasma by LC-MS/MS.
abstract: Henatinib maleate (R,Z)-2-[(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene) methyl]-5-(2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c] azepin-4-ketone maleate is a potent inhibitor of vascular endothelial growth factor receptors, and is currently under preclinical evaluation as an anticancer drug. A novel method for the quantification of henatinib maleate in rat plasma using high performance liquid chromatography-tandem mass spectrometry has been developed. The analyte (henatinib maleate) and internal standard (papaverine hydrochloride) were extracted from 50 microL of rat plasma by protein precipitation and separated on a C(18) column using a mixture of 25 mm ammonium acetate buffer : methanol : acetonitrile (35 : 50 : 15, v/v/v) as mobile phase with a run time of 4.5 min. The detection was performed by means of triple quadrupole mass spectrometer equipped with an ESI interface operating in the multiple-reaction monitoring mode. A linear response was observed over the concentration range 5.0-1000 ng/mL. The limit of quantification was 5.0 ng/mL. Both intra- and inter-day precision, defined as relative standard deviation, were within 9.7%. Accuracy, defined as relative error, was within +/- 3.1%. The developed method was successfully applied to preclinical pharmacokinetic studies of henatinib maleate in rat after a single oral administration of the drug.
authors: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China.
authors: Ping
authors: P
authors: Gu
authors: Ying
authors: Y
authors: Ding
authors: Dezhu
authors: D
authors: Sun
authors: Taijun
authors: T
authors: Hang
authors: Wenying
authors: W
authors: Liu
authors: Li
authors: L
authors: Ding
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001381:Azepines / Q000097:blood* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D007211:Indoles / Q000097:blood* / Q000737:chemistry; D016014:Linear Models; D008297:Male; D008298:Maleates / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010208:Papaverine / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; D007211:Indoles; D008298:Maleates; D010208:Papaverine; D040262:Receptors, Vascular Endothelial Growth Factor; C550539:2-((5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-5-(2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo(3,2-c)azepin-4-ketone