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Journal of Chinese Pharmaceutical Sciences ›› 2015, Vol. 24 ›› Issue (4): 217-224.DOI: 10.5246/jcps.2015.04.028

• Original articles • Previous Articles     Next Articles

Simultaneous determination of sunitinib and its active metabolites N-desethylsunitinib (SU12662) in nude mice plasma by liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study

Jingyun Li2, Jian Li2, Siyuan Wang2, Yin Yuan2, Qinghong Su2, Wei Lu1,2, Tianyan Zhou1,2*   

  1. 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China
    2. School of Pharmaceutical Science, Peking University Health Science Center, Beijing 100191, China
  • Received:2014-12-07 Revised:2015-01-13 Online:2015-04-28 Published:2015-01-30
  • Contact: Tel.: 86-10-82805937
  • Supported by:
    National Natural Science Foundation of China (NSFC, Grant No. 81473277).

Abstract:

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 sampleswere pre-treated by protein precipitation with pazopanib and used as an internal standard. Separation was performed on a reversedphase C18 column with a mobile phase composing of 10 mM ammonium formate pH 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 (r>0.99) 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.

Key words: LC-MS/MS, Sunitinib, SU12662, Nude mice, Pharmacokinetics

CLC Number: 

Supporting: