title: Development and application of a UPLC-MS/MS method for the pharmacokinetic study of 10-hydroxy camptothecin and hydroxyethyl starch conjugate in rats.
abstract: With the purpose to carry out the pharmacokinetic studies of 10-hydroxy camptothecin (10-HCPT) and hydroxyethyl starch (10-HCPT-HES) conjugate, an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated. The analytes, 10-HCPT and the internal standard, Diphenhydramine hydrochloride were extracted with ethyl acetate-isopropanol (95:5, v/v) and separated on an ACQUITY UPLC™ BEH C18 column using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) with a linear gradient program. With positive ion electrospray ionization (ESI), the analytes were monitored on a triple quadrupole mass spectrometer in the multiple reaction monitoring (MRM) mode. Linear calibration curves were obtained over the concentration ranges of 0.5-2500ng/mL. The intra- and inter-day precisions were less than 9.8% and 10.8%, respectively. The accuracy was within 12.1%. The mean recoveries of 10-HCPT at three concentrations of 2.5, 100, 2000ng/mL were higher than 87.2%. Commercial 10-HCPT injection and 10-HCPT-HES conjugate were administered intravenously at an equal dose of 10-HCPT at 0.5mg/kg. The biological half-life of conjugate was increased significantly from 10min to 3.15h and the bioavailability was 40 times higher than 10-HCPT injection. Consequently, the proposed UPLC-ESI-MS/MS method was proved to be sensitive, specific and reliable to analyze 10-HCPT in biological samples; 10-HCPT and HES conjugate is a promising strategy for delivery of 10-HCPT with prolonged half time and improved bioavailability.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Guofei
authors.initials: G
authors.lastname: Li
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.forename: Tianyang
authors.initials: T
authors.lastname: Ren
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006895:Hydroxyethyl Starch Derivatives / Q000097:blood* / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011786:Quality Control; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D006895:Hydroxyethyl Starch Derivatives; C028098:10-hydroxycamptothecin; D002166:Camptothecin
keywords: 10-HCPT; Conjugate; Pharmacokinetics; Rat plasma; UPLC–ESI-MS/MS