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

doi:10.5246/jcps.2015.04.028

Abstract

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:

R962

Supporting:

Jingyun Li, Jian Li, Siyuan Wang, Yin Yuan, Qinghong Su, Wei Lu, Tianyan Zhou. 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[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(4): 217-224.

References

[1] Mendel, D.B.; Laird, A.D.; Xin, X.; Louie, S.G.; Christensen, J.G.; Li, G.; Schreck, R.E.; Abrams, T.J.; Ngai, T.J.; Lee, L.B.; Murray, L.J.; Carver, J.; Chan, E.; Moss, K.G.; Haznedar, J.O.; Sukbuntherng, J.; Blake, R.A.; Sun, L.; Tang, C.; Miller, T.; Shirazian, S.; McMahon, G., Cherrington, J.M. Clin. Cancer Res. 2003, 9, 327-337.

[2] Abrams, T.J.; Lee, L.B.; Murray, L.J.; Pryer, N.K.; Cherrington, J.M. Mol. Cancer Ther. 2003, 2, 471-478.

[3] van Erp, N.P.; Gelderblom, H.; Guchelaar, H.J. Cancer Treat. Rev. 2009, 35, 692-706.

[4] Faivre, S.; Delbaldo, C.; Vera, K.; Robert, C.; Lozahic, S.; Lassau, N.; Bello, C.; Deprimo, S.; Brega, N.; Massimini, G.; Armand, J.P.; Scigalla, P.; Raymond, E. J. Clin. Oncol. 2006, 24, 25-35.

[5] Chouhan, J.D.; Zamarripa, D.E.; Lai, P.H.; Oramasionwu, C.U.; Grabinski, J.L. J. Oncol. Pharm. Pract. 2007, 13, 5-15.

[6] Varna, M.; Bousquet, G.; Ferreira, I.; Goulard, M.; El-Bouchtaoui, M.; Artus, P.M.; Verine, J.; de Kerviler, E.; Hernandez, E.; Leboeuf, C.; Escudier, B.; Legres, L.; Setterblad, N.; Soliman, H.; Feugeas, J.P.; Janin, A. Bertheau, P. Int. J. Clin. Exp. Pathol. 2014, 7, 2950-2962.

[7] Li, X.; Tong, L.J.; Ding, J.; Meng, L.H. Cancer Lett. 2014, 342, 159-166.

[8] Schem, C.; Bauerschlag, D.; Bender, S.; Lorenzen, A.C.; Loermann, D.; Hamann, S.; Rosel, F.; Kalthoff, H.; Gluer, C.C.; Jonat, W.; Tiwari, S. BMC Cancer. 2013, 13, 32.

[9] Fratto, M.E.; Imperatori, M.; Vincenzi, B.; Tomao, F.; Santini, D.; Tonini, G. Clin. Ter. 2010, 161, 475-482.

[10] Abdel-Aziz, A.K.; Shouman, S.; El-Demerdash, E.; Elgendy, M.; Abdel-Naim, A.B. Chem. Biol. Interact. 2014, 217, 28-40.

[11] Lopergolo, A.; Nicolini, V.; Favini, E.; Dal Bo, L.; Tortoreto, M.; Cominetti, D.; Folini, M.; Perego, P.; Castiglioni, V.; Scanziani, E.; Borrello, M.G.; Zaffaroni, N.; Cassinelli, G.; Lanzi, C. J. Clin. Endocrinol. Metab. 2014, 99, 498-509.

[12] Choo, E.F.; Ng, C.M.; Berry, L.; Belvin, M.; Lewin-Koh, N.; Merchant, M.; Salphati, L. Cancer Chemother. Pharmacol. 2013, 71, 133-143.

[13] Li, M.; Li, H.; Cheng, X.; Wang, X.; Li, L.; Zhou, T.; Lu, W. Pharm. Res. 2013, 30, 1400-1408.

[14] Yamazaki, S. AAPS J. 2013, 15, 354-366.

[15] Bello, C.L.; Sherman, L.; Zhou, J.; Verkh, L.; Smeraglia, J.; Mount, J.; Klamerus, K.J. Anticancer Drugs. 2006, 17, 353-358.

[16] Baratte, S.; Sarati, S.; Frigerio, E.; James, C.A.; Ye, C.; Zhang, Q. J. Chromatogr. A. 2004, 1024, 87-94.

[17] Etienne-Grimaldi, M.C.; Renee, N.; Izzedine, H.; Milano, G. J. Chromatogr. B. 2009, 877, 3757-3561.

[18] de Bruijn, P.; Sleijfer, S.; Lam, M.H.; Mathijssen, R.H.; Wiemer, E.A.; Loos, W.J. J. Pharm. Biomed. Anal. 2010, 51, 934-941.

[19] Rodamer, M.; Elsinghorst, P.W.; Kinzig, M.; Gutschow, M.; Sorgel, F. J. Chromatogr. B. 2011, 879, 695-706.

[20] Qiu, F.; Bian, W.; Li, J.; Ge, Z. Biomed. Chromatogr. 2013, 27, 615-621.

[21] Lankheet, N.A.; Steeghs, N.; Rosing, H.; Schellens, J.H.; Beijnen, J.H.; Huitema, A.D. Ther. Drug Monit. 2013, 35, 168-176.

[22] Chen, X.; Wang, Z.; Liu, M.; Liao, M.; Wang, X.; Du, H.; Chen, J.; Yao, M.; Li, Q. Biomed. Chromatogr. 2014. doi: 10.1002/bmc.3331

[23] Food and Drug Administration. Guidance for Industry: Bioanalytical Method Validation. US Department of Health and Human Services, CDER and CVM: Rockville, MD 2001.

[24] Yuan, Y.; Zhou, X.; Li, J.; Ye, S.; Ji, X.; Li, L.; Zhou, T.; Lu, W. Biomed Chromatogr. 2014, 29, 578-583.

[25] Cheng, X.; Guo, L.; Li, Z.; Li, L.; Zhou, T; Lu, W. J. Chromatogr. B. 2013, 64-70, 915-916.

[26] Li, M.; Wu, Q.; Li, H.; Ning, M.; Chen, Y.; Li, L.; Zhou, T.; Lu, W. J. Chin. Pharm. Sci. 2012, 21, 296-303.

[27] Sistla, A.; Shenoy, N. Drug Dev. Ind. Pharm. 2005, 31, 1001-1007.

[28] Sistla, A.; Yang, W.L.; Shenoy, N. J. Chromatogr. A. 2006, 1110, 73-80.

[29] Zhou, Q.; Gallo, J.M. J. Pharm. Biomed. Anal. 2010, 51, 958-964.