A new and sensitive liquid chromatography-tandem mass spectrometry method was developed for the determination of SM-1 in rat plasma. After a simple protein precipitation, SM-1 and internal standard （gefitinib） were ...A new and sensitive liquid chromatography-tandem mass spectrometry method was developed for the determination of SM-1 in rat plasma. After a simple protein precipitation, SM-1 and internal standard （gefitinib） were separated with gradient elution on a Waters XBridge C18 （50 mm×4.6 mm, 3.5μm） using acetonitrile-methanol-10 mM ammonium acetate （37.5：37.5：25, v/v/v） as mobile phase. The triple quadruple mass spectrometer was set in positive electrospray ionization mode, multiple reaction monitoring was used for quantification. The precursors to produce ion transitions monitored for SM-1 and IS were m/z 407.3→203.4 and 447.3→128.3, respectively. The method validation was conducted over the curve range of 30-6000 ng/mL. The intra- and inter-day precisions were less than 4.7%, the average extraction recoveries ranged from 98.7% to 104.1% for each analyte. SM-1 was proved to be stable during sample storage preparation and analytical procedures. All the results met the acceptance criteria in accordance with the FDA guidance for bioanalytical method. Consequently, this method was successfully applied to determine SM-1 concentrations in rats after oral administrations at the doses of 200, 100 and even 50 mg/kg.展开更多
基金National Science and Technology Major Projects(Grant No.2012ZX09103101-051)China Postdoctoral Science Fou ndation Funded Projects(Grant No.2017M612599)Scientific Re search Foundation for Postdoctoral of Central South University(Grant No.140050005)
文摘A new and sensitive liquid chromatography-tandem mass spectrometry method was developed for the determination of SM-1 in rat plasma. After a simple protein precipitation, SM-1 and internal standard （gefitinib） were separated with gradient elution on a Waters XBridge C18 （50 mm×4.6 mm, 3.5μm） using acetonitrile-methanol-10 mM ammonium acetate （37.5：37.5：25, v/v/v） as mobile phase. The triple quadruple mass spectrometer was set in positive electrospray ionization mode, multiple reaction monitoring was used for quantification. The precursors to produce ion transitions monitored for SM-1 and IS were m/z 407.3→203.4 and 447.3→128.3, respectively. The method validation was conducted over the curve range of 30-6000 ng/mL. The intra- and inter-day precisions were less than 4.7%, the average extraction recoveries ranged from 98.7% to 104.1% for each analyte. SM-1 was proved to be stable during sample storage preparation and analytical procedures. All the results met the acceptance criteria in accordance with the FDA guidance for bioanalytical method. Consequently, this method was successfully applied to determine SM-1 concentrations in rats after oral administrations at the doses of 200, 100 and even 50 mg/kg.
