A sensitive, rapid, and simple liquid chromatography tandem mass spectrometry(LC-MS/MS) method for simultaneous determination of sunitinib and its active metabolites in plasma of BABL/c nude mice was developed and v...A sensitive, rapid, and simple liquid chromatography tandem mass spectrometry(LC-MS/MS) method for simultaneous determination of sunitinib and its active metabolites in plasma of BABL/c nude mice was developed and validated. Plasma samples were pre-treated by protein precipitation with pazopanib and used as an internal standard. Separation was performed on a reversed phase C18 column with a mobile phase composing of 10 m M ammonium formate p H 3.25(adjusted with formic acid) and acetonitrile(65:35, v/v) at a flow rate of 0.5 mL /min. Triple quadrupole tandem mass in multiple reaction monitoring(MRM) mode with electrospray positive ionization was used to monitor all the compounds. The current LC-MS/MS method was highly selective and sensitive with lowest limit of quantitation(LLOQ) of 0.5 ng/mL for both analytes and reliable intra- and inter-day precision and accuracy validated by relative error(RE%) and relative standard deviation(RSD%). Linearity of calibration curve was excellent(r0.99) within a concentration range of 0.5–1000 ng/mL. This method was successfully applied to a pharmacokinetics study on BABL/c nude mice given with single dose of oral administration of sunitinib at 20 mg/kg.展开更多
基金National Natural Science Foundation of China(NSFC,Grant No.81473277)
文摘A sensitive, rapid, and simple liquid chromatography tandem mass spectrometry(LC-MS/MS) method for simultaneous determination of sunitinib and its active metabolites in plasma of BABL/c nude mice was developed and validated. Plasma samples were pre-treated by protein precipitation with pazopanib and used as an internal standard. Separation was performed on a reversed phase C18 column with a mobile phase composing of 10 m M ammonium formate p H 3.25(adjusted with formic acid) and acetonitrile(65:35, v/v) at a flow rate of 0.5 mL /min. Triple quadrupole tandem mass in multiple reaction monitoring(MRM) mode with electrospray positive ionization was used to monitor all the compounds. The current LC-MS/MS method was highly selective and sensitive with lowest limit of quantitation(LLOQ) of 0.5 ng/mL for both analytes and reliable intra- and inter-day precision and accuracy validated by relative error(RE%) and relative standard deviation(RSD%). Linearity of calibration curve was excellent(r0.99) within a concentration range of 0.5–1000 ng/mL. This method was successfully applied to a pharmacokinetics study on BABL/c nude mice given with single dose of oral administration of sunitinib at 20 mg/kg.