title: Development and validation of a highly rapid and sensitive LC-MS/MS method for determination of SZ-685C, an investigational marine anticancer agent, in rat plasma--application to a pharmacokinetic study in rats.
abstract: A sensitive and rapid method was developed and validated for the quantitative analysis of the novel anticancer agent SZ-685C in rat plasma using high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) in negative ion mode in order to support the following pre-clinical and clinical studies. SZ-685C and the internal standard (IS, emodin) were extracted from rat plasma by a simple liquid-liquid extraction technique using ethyl acetate as extraction solvent. Chromatographic separation was performed on an Elite Hypersil BDS C18 column (100 mm × 2.1 mm i.d., 3 μm). Elution was carried out using methanol/acetonitrile/2mM ammonium formate (pH 4) (80:15:5 (v/v/v)) at a flow-rate of 0.3 mL/min with a run time of 2.5 min. This assay was linear over a concentration range of 50-10,000 ng/mL with a lower limit of quantification of 50 ng/mL. The intra- and inter-batch precision was less than 15% for all quality control samples at concentrations of 100, 1000 and 7500 ng/mL. These results indicate that the method was efficient with a short run time and acceptable accuracy, precision and sensitivity. This method was successfully applied to explore pharmacokinetics of SZ-685C in rats after oral and intravenous administration of this agent. The absolute bioavailability is about 54.8-66.8% and the t(1/2) is 5.7-9.2h, these results provide basic information for further comprehensive pre-clinical research.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Jiang-Ying
authors.initials: JY
authors.lastname: Chen
authors.forename: Xue-Ding
authors.initials: XD
authors.lastname: Wang
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Zhong
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Qin
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Li
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Huang
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.forename: Meng-Feng
authors.initials: MF
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000097:blood* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D004642:Emodin / Q000032:analysis / Q000737:chemistry; D005260:Female; D005658:Fungi / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D043982:Rhizophoraceae / Q000382:microbiology; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D004642:Emodin