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.
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References
D. B. Kaufman, Am. J. Transplant., 2004, 4, 38.
A. L. Taylor, Crit. Rev. Oncol. Hemat., 2005, 56, 23.
C. Reichel, M. V. Falkenhausen, D. Brockmeier, and H. J. Dengler, Eur. J. Clin. Pharmacol., 1994, 46, 417.
D. W. Holt, A. Johnston, N. B. Roberts, J. M. Tredger, and A. K. Trull, Ann. Clin. Biochem., 1994, 31, 420.
E. Schutz, D. Svinarov, M. Shipkova, P. D. Niedmann, V. W. Armstrong, and E. Wieland, Clin. Chem., 1998, 44, 2158.
W. Steimer, Clin. Chem., 1999, 45, 371.
A. Hamwi, M. Veitl, G. Manner, K. Ruzicka, C. Schweiger, and T. Szekeres, Am. J. Clin. Pathol., 1999, 112, 358.
A. R. Terrell, T. M. Daly, K. G. Hock, D. C. Kilgore, T. Q. Wei, and S. Hernandez, Clin. Chem., 2002, 48, 1059.
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.
P. Salm, P. J. Taylor, S. V. Lynch, C. R. Warnholtz, and P. I. Pillans, Clin. Biochem., 2005, 38, 667.
N. Brignol and L. M. McMahon, Rapid Commun. Mass Spectrom., 2001, 15, 898.
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.
M. A. Poquette, G. L. Lensmeyer, and T. C. Doran, Ther. Drug Monit., 2005, 27, 144.
F. Streit, Clin. Chem., 2002, 48, 955.
M. Deters, G. Kirchner, K. Resch, and V. Kaever, Clin. Chem. Lab. Med., 2002, 40, 285.
T. Koal, M. Deters, B. Casetta, and V. Kaever, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci., 2004, 805, 215.
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.
K. Nozomu, Rapid Commun. Mass Spectrom., 2006, 20, 733.
B. Hana, P. Ilona, H. Petra, and G. Milan, J. Sep. Sci., 2010, 33, 2287.
P. Falck, H. Guldseth, A. Asberg, K. Midtvedt, and J. L. E. Reubsaet, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci., 2007, 852, 345.
B. Vollenbroeker, J. H. Koch, M. Fobker, B. Suwelack, H. Hohage, and U. Muller, Transplant. Proc., 2005, 37, 1741.
Y. Wu and J. R. Engen, J. Am. Soc. Mass Spectrom., 2006, 17, 163.
J. Wang, H. Li, C. Jin, and X. Xiao, J. Pharm. Biomed. Anal., 2008, 47, 765.
S. Pedraglio, M. G. Rozio, P. Misiano, V. Reali, G. Dondio, and C. Bigogno, J. Pharm. Biomed. Anal., 2007, 44, 665.
J. M. Kovarik, E. A. Mueller, A. Johnston, G. Hitzenberger, and K. Kutz, Pharmacotherapy, 1993, 13, 613.
J. M. Kovarik, D. Barilla, L. McMahon, Y. Wang, J. Kisicki, and R. Schmouder, Clin. Transplant., 2002, 16, 306.
F. Kees, M. Bucher, F. Schweda, H. Gschaidmeier, L. Faerber, and R. Seifert, Naunyn-Schmiedeberg’s Arch. Pharmacol., 2007, 375, 393.
T. Chang, L. Z. Benet, and M. F. Hebert, Clin. Pharmacol. Ther., 1996, 59, 297.
L. Nováková, L. Matysová, and P. Solich, Talanta, 2006, 68, 908.
D. A. Whitman, V. Abbott, and K. Fregien, Ther. Drug Monit., 1993, 15, 552.
L. M. McMahon, S. Luo, M. Hayes, and F. L. Tse, Rapid Commun. Mass Spectrom., 2000, 14, 1965.
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.
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.
R. D. Kulkarni, L. Ramamurthy, B. Chauhan, S. Patel, V. U. Baghel, A. Singh, and D. R. Sharma, Indian J. Pharmacol., 2001, 33, 394.
Y. Yang and C. C. Hodges, Assay transfer from HPLC to UPLC for higher analysis throughput, http://www.chromatographyonline.com, 2005.
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.
KFDA, Bioanalytical method validation, National Institute of Toxicology Research, http://eng.kfda.go.kr/index.php, 2003.
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H. J. J. and M.-R. G. equally contributed to this work.
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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
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DOI: https://doi.org/10.2116/analsci.30.293