Skip to main content

Advertisement

Log in

Quantitative Determination of Cyclosporine in Human Whole Blood by Ultra-Performance Liquid Chromatography with Triple Quadrupole Tandem Mass Spectrometry

  • Published:
Analytical Sciences Aims and scope Submit manuscript

Abstract

Cyclosporine is an immunosuppressant drug used in organ transplants or for the treatment of autoimmune diseases. We developed and validated a simple, sensitive, and specific method using UPLC-MS/MS to determine cyclosporine levels in human whole blood. MS/MS detection was performed in the positive electrospray ionization mode with multiple reaction monitoring. Cyclosporine was extracted from whole-blood samples using ascomycin as an internal standard. The mass transitions m/z 1203.49 → 1185.53 and m/z 814.71 → 796.67 were used to assay the analyte and IS. This method was validated with respect to linearity, specificity, accuracy, precision, recovery, and stability. The method exhibited a linear response from 10 to 1000 ng mL-1 with correlation coefficient values >0.99. The precision and the accuracy values were within 15%, except at the lower limit of quatification (LLOQ). Cyclosporine was stable in whole blood with no evidence of degradation. This method was successfully applied to a pharmacokinetic study of cyclosporine in healthy volunteers following oral administration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. D. B. Kaufman, Am. J. Transplant., 2004, 4, 38.

    Article  PubMed  Google Scholar 

  2. A. L. Taylor, Crit. Rev. Oncol. Hemat., 2005, 56, 23.

    Article  Google Scholar 

  3. C. Reichel, M. V. Falkenhausen, D. Brockmeier, and H. J. Dengler, Eur. J. Clin. Pharmacol., 1994, 46, 417.

    Article  CAS  PubMed  Google Scholar 

  4. D. W. Holt, A. Johnston, N. B. Roberts, J. M. Tredger, and A. K. Trull, Ann. Clin. Biochem., 1994, 31, 420.

    Article  PubMed  Google Scholar 

  5. E. Schutz, D. Svinarov, M. Shipkova, P. D. Niedmann, V. W. Armstrong, and E. Wieland, Clin. Chem., 1998, 44, 2158.

    Article  CAS  PubMed  Google Scholar 

  6. W. Steimer, Clin. Chem., 1999, 45, 371.

    Article  CAS  PubMed  Google Scholar 

  7. A. Hamwi, M. Veitl, G. Manner, K. Ruzicka, C. Schweiger, and T. Szekeres, Am. J. Clin. Pathol., 1999, 112, 358.

    Article  CAS  PubMed  Google Scholar 

  8. A. R. Terrell, T. M. Daly, K. G. Hock, D. C. Kilgore, T. Q. Wei, and S. Hernandez, Clin. Chem., 2002, 48, 1059.

    Article  CAS  PubMed  Google Scholar 

  9. P. J. Taylor, C. E. Jones, P. T. Martin, S. V. Lynch, A. G. Johnson, and S. M. Pond, J. Chromatogr. B: Anal. Technol. Biomed. Sci. Appl., 1998, 705, 289.

    Article  CAS  Google Scholar 

  10. P. Salm, P. J. Taylor, S. V. Lynch, C. R. Warnholtz, and P. I. Pillans, Clin. Biochem., 2005, 38, 667.

    Article  CAS  PubMed  Google Scholar 

  11. N. Brignol and L. M. McMahon, Rapid Commun. Mass Spectrom., 2001, 15, 898.

    Article  CAS  PubMed  Google Scholar 

  12. M. F. Hebert, R. W. Townsend, S. Austin, G. Balan, D. K. Blough, D. Buell, J. Keirns, and I. Bekersky, J. Clin. Pharmacol., 2005, 45, 954.

    Article  CAS  PubMed  Google Scholar 

  13. M. A. Poquette, G. L. Lensmeyer, and T. C. Doran, Ther. Drug Monit., 2005, 27, 144.

    Article  CAS  PubMed  Google Scholar 

  14. F. Streit, Clin. Chem., 2002, 48, 955.

    Article  CAS  PubMed  Google Scholar 

  15. M. Deters, G. Kirchner, K. Resch, and V. Kaever, Clin. Chem. Lab. Med., 2002, 40, 285.

    Article  CAS  PubMed  Google Scholar 

  16. T. Koal, M. Deters, B. Casetta, and V. Kaever, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci., 2004, 805, 215.

    Article  CAS  Google Scholar 

  17. U. Christians, W. Jacobsen, N. Serkova, L. Z. Benet, C. Vidal, K. F. Sewing, M. P. Manns, and G. I. Kirchner, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci., 2000, 748, 41.

    Article  CAS  Google Scholar 

  18. K. Nozomu, Rapid Commun. Mass Spectrom., 2006, 20, 733.

    Article  Google Scholar 

  19. B. Hana, P. Ilona, H. Petra, and G. Milan, J. Sep. Sci., 2010, 33, 2287.

    Article  Google Scholar 

  20. P. Falck, H. Guldseth, A. Asberg, K. Midtvedt, and J. L. E. Reubsaet, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci., 2007, 852, 345.

    Article  CAS  Google Scholar 

  21. B. Vollenbroeker, J. H. Koch, M. Fobker, B. Suwelack, H. Hohage, and U. Muller, Transplant. Proc., 2005, 37, 1741.

    Article  CAS  PubMed  Google Scholar 

  22. Y. Wu and J. R. Engen, J. Am. Soc. Mass Spectrom., 2006, 17, 163.

    Article  CAS  PubMed  Google Scholar 

  23. J. Wang, H. Li, C. Jin, and X. Xiao, J. Pharm. Biomed. Anal., 2008, 47, 765.

    Article  CAS  PubMed  Google Scholar 

  24. S. Pedraglio, M. G. Rozio, P. Misiano, V. Reali, G. Dondio, and C. Bigogno, J. Pharm. Biomed. Anal., 2007, 44, 665.

    Article  CAS  PubMed  Google Scholar 

  25. J. M. Kovarik, E. A. Mueller, A. Johnston, G. Hitzenberger, and K. Kutz, Pharmacotherapy, 1993, 13, 613.

    CAS  PubMed  Google Scholar 

  26. J. M. Kovarik, D. Barilla, L. McMahon, Y. Wang, J. Kisicki, and R. Schmouder, Clin. Transplant., 2002, 16, 306.

    Article  PubMed  Google Scholar 

  27. F. Kees, M. Bucher, F. Schweda, H. Gschaidmeier, L. Faerber, and R. Seifert, Naunyn-Schmiedeberg’s Arch. Pharmacol., 2007, 375, 393.

    Article  CAS  Google Scholar 

  28. T. Chang, L. Z. Benet, and M. F. Hebert, Clin. Pharmacol. Ther., 1996, 59, 297.

    Article  CAS  PubMed  Google Scholar 

  29. L. Nováková, L. Matysová, and P. Solich, Talanta, 2006, 68, 908.

    Article  PubMed  Google Scholar 

  30. D. A. Whitman, V. Abbott, and K. Fregien, Ther. Drug Monit., 1993, 15, 552.

    Article  CAS  PubMed  Google Scholar 

  31. L. M. McMahon, S. Luo, M. Hayes, and F. L. Tse, Rapid Commun. Mass Spectrom., 2000, 14, 1965.

    Article  CAS  PubMed  Google Scholar 

  32. W. Tszyrsznic, A. Borowiec, E. Pawlowska, R. Jazwiec, D. Zochowska, I. Bartlomiejczyk, J. Zegarska, L. Paczek, and M. Dadlez, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci., 2013, 9, 928.

    Google Scholar 

  33. A. J. Bergman, J. Burke, P. Larson, L. Reyderman, P. Statkevich, T. Kosoglou, H. E. Greenberg, W. K. Kraft, G. Frick, G. Murphy, K. Gottesdiener, and J. F. Paolini, J. Clin. Pharmacol., 2006, 46, 321.

    Article  CAS  PubMed  Google Scholar 

  34. R. D. Kulkarni, L. Ramamurthy, B. Chauhan, S. Patel, V. U. Baghel, A. Singh, and D. R. Sharma, Indian J. Pharmacol., 2001, 33, 394.

    Google Scholar 

  35. Y. Yang and C. C. Hodges, Assay transfer from HPLC to UPLC for higher analysis throughput, http://www.chromatographyonline.com, 2005.

  36. FDA, Guidance for industry, bioanalytical method validation, US Department of Health and Human Services, Center for Drug Evaluation and Research (CDER), http://www.fda.gov/cder/guidance, 2001.

  37. KFDA, Bioanalytical method validation, National Institute of Toxicology Research, http://eng.kfda.go.kr/index.php, 2003.

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hae Won Lee or Young-Ran Yoon.

Additional information

H. J. J. and M.-R. G. equally contributed to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jung, H.J., Gwon, MR., Park, J. et al. Quantitative Determination of Cyclosporine in Human Whole Blood by Ultra-Performance Liquid Chromatography with Triple Quadrupole Tandem Mass Spectrometry. ANAL. SCI. 30, 293–298 (2014). https://doi.org/10.2116/analsci.30.293

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2116/analsci.30.293

Keywords

Navigation