DOI QR코드

DOI QR Code

Rapid Quantification of Topotecan in Biological Samples by Liquid Chromatography/Tandem Mass Spectrometry

  • Published : 2009.10.20

Abstract

A rapid liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay method was developed for the determination of topotecan levels in rat serum. The assay utilized a single liquid-liquid extraction with a mixture of ethy l acetate and acetonitrile (6:1 v/v) and isocratic elution. The multiple reaction monitoring was based on the transition of m/z 422.0$\rightarrow$376.5 for topotecan and 315.1$\rightarrow$226.6 for clomipramine (internal standard). The developed assay was validated to demonstrate the specificity, recovery, lower limit of quantification (LLOQ), accuracy and precision. The assay was linear over a concentration range from 0.5-100 ng/mL, with LLOQ being 0.5 ng/mL using a small volume of rat serum (0.1 mL). The mean intra- and inter-day assay accuracy was 87.7-111.0% and 97.8-108.3, respectively, and the mean intra- and interday precision was between 1.6-4.3% and 3.8-10.3, respectively. The developed assay was applied to a pharmacokinetic study after a bolus i.v. injection of topotecan in rats.

Keywords

References

  1. D. Costin and M. Potmesil, Preclinical and clinical development of camptothecins, Adv. Pharmacol., 29B, 51-72 (1994). https://doi.org/10.1016/S1054-3589(08)61131-X
  2. G.J. Creemers, B. Lund, J. Verweij, Topoisomerase I inhibitors: topotecan and irinotecan, Cancer Treat. Rev., 20, 73-96 (1994). https://doi.org/10.1016/0305-7372(94)90011-6
  3. C.J. Gerrits, M.J. de Jonge, J.H. Schellens, G. Stoter and J. Verweij, Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development, Br. J. Cancer, 76, 952-962 (1997). https://doi.org/10.1038/bjc.1997.491
  4. V.M. Herben, W.W. ten Bokkel Huinink and J.H. Beijnen, Clinical pharmacokinetics of topotecan, Clin. Pharmacokinet., 31, 85-102 (1996). https://doi.org/10.2165/00003088-199631020-00001
  5. R.K. Johnson, R.P. Hertzberg, W.D. Kingsbury, J.C. Boehm, M.J. Caranfa, L.F., Faucette, F. L. McCabe and K.G. Holden, Proceeding of the sixth NCIEORTC symposium on new drugs in cancer therapy, 301 (1989).
  6. W.D. Kingsbury, J.C. Boehm, D.R. Jakas, K.G. Holden, S.M. Hecht, G. Gallagher, M.J. Caranfa, F.L. McCabe, L.F. Faucette and R.K. Johnson, Synthesis of water-soluble (aminoalkyl) camptothecin analogues: inhibition of topoisomerase I and antitumor activity, J. Med. Chem., 34, 98-107 (1991). https://doi.org/10.1021/jm00105a017
  7. H.A. Burris 3rd, A.R. Hanauske, R.K. Johnson, M.H. Marshall, J.G. Kuhn, S.G. Hilsenbeck and D.D. Von Hoff, Activity of topotecan, a new topoisomerase I inhibitor, against human tumor colony-forming units in vitro, J. Natl. Cancer Inst., 84, 1816-1820 (1992). https://doi.org/10.1093/jnci/84.23.1816
  8. S.C. Plaxe, R.D. Christen, J. O'Quigley, P.S. Braly, J.L. Freddo, E. McClay, D. Heath and S.B. Howell, Phase I and pharmacokinetic study of intraperitoneal topotecan, Invest. New Drugs, 16, 147-153 (1998). https://doi.org/10.1023/A:1006045125018
  9. L.S. Hofstra, A.M. Bos, E.G. de Vries, A.G. van der Zee, J.H. Beijnen, H. Rosing, H.N. Mulder, J.G. Aalders and P.H. Willemse, A phase I and pharmacokinetic study of intraperitoneal topotecan, Br. J. Cancer., 85, 1627-1633 (2001). https://doi.org/10.1054/bjoc.2001.2161
  10. R.P. Hertzberg, M.J. Caranfa, K.G. Holden, D.R. Jakas, G. Gallagher, M.R. Mattern, S.M. Mong, J.O. Bartus, R.K. Johnson and W.D. Kingsbury, Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity, J. Med. Chem., 32, 715-720 (1989). https://doi.org/10.1021/jm00123a038
  11. C.F. Stewart, W.C. Zamboni, W.R. Crom, A. Gajjar, R.L. Heideman, W.L. Furman, W.H. Meyer, P.J. Houghton and C.B. Pratt, Topoisomerase I interactive drugs in children with cancer, Invest. New Drug, 14, 37-47 (1996). https://doi.org/10.1007/BF00173681
  12. T. Yamagata and H. Kusuhara, M. Morishita, K. Takayama, H. Benameur, Y. Sugiyama, Improvement of the oral drug absorption of topotecan through the inhibition of intestinal xenobiotic efflux transporter, breast cancer resistance protein, by excipients, Drug Metab. Dispos., 35, 1142-1148 (2007). https://doi.org/10.1124/dmd.106.014217
  13. J. Shen, A.M. Carcaboso, K.E. Hubbard, M. Tagen, H.G. Wynn, J.C. Panetta, C.M. Waters, M.A. Elmeliegy and C.F. Stewart, Compartment-specific roles of ATP-binding cassette transporters define differential topotecan distribution in brain parenchyma and cerebrospinal fluid, Cancer Res., 69, 5885- 5892 (2009). https://doi.org/10.1158/0008-5472.CAN-09-0700
  14. Y. Su, P. Hu , S.H. Lee and P.J. Sinko, Using novobiocin as a specific inhibitor of breast cancer resistant protein to assess the role of transporter in the absorption and disposition of topotecan, J. Pharm. Pharm. Sci., 10, 519-36 (2007).
  15. N.A. de Vries, J. Zhao, E. Kroon, T. Buckle, J.H. Beijnen and O. van Tellingen, P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan, Clin. Cancer Res., 13, 6440-6449 (2007). https://doi.org/10.1158/1078-0432.CCR-07-1335
  16. S. Zhang, X. Wang, K. Sagawa and M.E. Morris, Flavonoids chrysin and benzoflavone, potent breast cancer resistance protein inhibitors, have no significant effect on topotecan pharmacokinetics in rats or mdr1a/1b (-/-) mice, Drug Metab. Dispos., 33, 341-348 (2005). https://doi.org/10.1124/dmd.104.002501
  17. J.H. Beijnen, B.R. Smith, W.J. Keijer, R. van Gijn, W.W. ten Bokkel Huinink, L.T. Vlasveld, S. Rodenhuis and W.J. Underberg, High-performance liquid chromatographic analysis of the new antitumor drug SK&F 104864-A (NSC 609699) in plasma, J. Pharm. Biomed. Anal., 8, 789-794 (1990). https://doi.org/10.1016/0731-7085(90)80122-6
  18. W.J. Loos, G. Stoter, J. Verweij and J.H. Schellens, Sensitive high-performance liquid chromatographic fluorescence assay for the quantitation of topotecan (SKF 104864-A) and its lactone ring-opened product (hydroxy acid) in human plasma and urine, J. Chromatogr. B Biomed. Appl., 678, 309-315 (1996). https://doi.org/10.1016/0378-4347(95)00529-3
  19. H. Rosing, D.M. van Zomeren, E. Doyle, W.W. ten Bokkel, J.H. Schellens, A. Bult and J.H. Beijnen, Quantification of topotecan and its metabolite N-desmethyltopotecan in human plasma, urine and faeces by high-performance liquid chromatographic methods, J. Chromatogr. B Biomed. Sci. Appl., 727, 191-203 (1999). https://doi.org/10.1016/S0378-4347(99)00078-X
  20. J. Chen and J.P. Balthasar, High-performance liquid chromatographic assay for the determination of total and free topotecan in the presence and absence of anti-topotecan antibodies in mouse plasma, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 816, 183-192 (2005). https://doi.org/10.1016/j.jchromb.2004.11.035