Journal of Korean Society for Clinical Pharmacology and Therapeutics (임상약리학회지)

Korean Society for Clinical Pharmacology and Therapeutics (대한임상약리학회)
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Validation of LC-MS/MS Method for Determination of Bivalirudin in Human Plasma: Application to a Pharmacokinetic Study

사람 혈장에서 비발리루딘 농도 측정을 위한 분석 방법의 유효성 검증 및 약동학 시험에의 적용

  • Kim, Yo Han (Department of Clinical Pharmacology and Therapeutics, Asan Medical Center) ;
  • Park, Hyun Jeong (Clinical Trial Center, Asan Medical Center) ;
  • Choi, Hee Youn (Department of Clinical Pharmacology and Therapeutics, Asan Medical Center) ;
  • Lim, Hyeong-Seok (Department of Clinical Pharmacology and Therapeutics, Asan Medical Center) ;
  • Bae, Kyun-Seop (Department of Clinical Pharmacology and Therapeutics, Asan Medical Center)
  • 김요한 (서울아산병원 임상약리학과) ;
  • 박현정 (서울아산병원 임상시험센터 임상약리실험실) ;
  • 최희연 (서울아산병원 임상약리학과) ;
  • 임형석 (서울아산병원 임상약리학과) ;
  • 배균섭 (서울아산병원 임상약리학과)
  • Received : 2013.11.14
  • Accepted : 2013.12.20
  • Published : 2013.12.31
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Abstract

Background: Bivalirudin is a direct thrombin inhibitor for patients with unstable angina undergoing percutaneous coronary intervention. Methods: A sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of bivalirudin, in human plasma using nafarelin as internal standard (IS). Chromatographic separation was performed using a Shiseido MG3 mm column ($2.0{\times}50$ mm) with a gradient mobile phase consisting of water and acetonitrile containing 0.1 % formic acid at a flow rate of 0.4 mL/min, and total run time was within 5 min. Detection and quantification was performed by the mass spectrometer using a multiple reaction-monitoring mode at m/z $1091.0{\rightarrow}650.3$ for bivalirudin, and m/z $662.1{\rightarrow}249.3$ for IS. Results: The assay was linear over a concentration range of 10 - 10000 ng/mL with a lower limit of quantification of 10 ng/mL in human plasma. Conclusion: This method was successfully applied for pharmacokinetics study after intravenous administration of bivalirudin to healthy Korean male volunteers.

Keywords

References

  1. Gladwell TD. Bivalirudin: a direct thrombin inhibitor. Clin Ther, 2002;24(1):38-58.
  2. Lincoff AM, Bittl JA, Harrington RA, Feit F, Kleiman NS, Jackman JD, Sarembock IJ, Cohen DJ, Spriggs D, Ebrahimi R, Keren G, Carr J, Cohen EA, Betriu A, Desmet W, Kereiakes DJ, Rutsch W, Wilcox RG, de Feyter PJ, Vahanian A, Topol EJ, Investigators R-. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA, 2003;289(7):853-863. https://doi.org/10.1001/jama.289.7.853
  3. EMEA. Scientific discussion for the approval of Bivalirudin [cited 2013 31 Oct]. Available from: http://www.ema.europa.eu/docs/en_GB/document_ library/EPAR_-_Scientific_Discussion/human/ 000562/WC500025072.pdf.
  4. FDA. NDA 020873 Angiomax (Bivalirudin): Clinical Pharmacology Biopharmaceutics Review. Rockville, MD: Department of Health and Human Services, US Food and Drug Administration; 2003.
  5. Robson R, White H, Aylward P, Frampton C. Bivalirudin pharmacokinetics and pharmacodynamics: effect of renal function, dose, and gender. Clin Pharmacol Ther, 2002;71(6):433-439. https://doi.org/10.1067/mcp.2002.124522
  6. Lidon RM, Theroux P, Juneau M, Adelman B, Maraganore J. Initial experience with a direct antithrombin, Hirulog, in unstable angina. Anticoagulant, antithrombotic, and clinical effects. Circulation, 1993;88(4 Pt 1):1495-1501. https://doi.org/10.1161/01.CIR.88.4.1495
  7. Topol EJ, Bonan R, Jewitt D, Sigwart U, Kakkar VV, Rothman M, de Bono D, Ferguson J, Willerson JT, Strony J, et al. Use of a direct antithrombin, hirulog, in place of heparin during coronary angioplasty. Circulation, 1993;87(5):1622-1629. https://doi.org/10.1161/01.CIR.87.5.1622
  8. Reed MD, Bell D. Clinical pharmacology of bivalirudin. Pharmacotherapy, 2002;22(6 Pt 2): 105S-111S. https://doi.org/10.1592/phco.22.10.105S.33616
  9. Anand SX, Viles-Gonzalez JF, Mahboobi SK, Heerdt PM. Bivalirudin utilization in cardiac surgery: shifting anticoagulation from indirect to direct thrombin inhibition. Can J Anaesth, 2011;58(3):296-311. https://doi.org/10.1007/s12630-010-9423-0
  10. Shammas NW. Bivalirudin: pharmacology and clinical applications. Cardiovasc Drug Rev, 2005;23(4):345-360.
  11. Pan G, Wang X, Huang Y, Gao X, Wang Y. Development and validation of a LC-MS/MS method for determination of bivalirudin in human plasma: Application to a clinical pharmacokinetic study. J Pharm Biomed Anal, 2010;52(1):105-109. https://doi.org/10.1016/j.jpba.2009.12.002
  12. Farthing D, Larus T, Fakhry I, Gehr T, Prats J, Sica D. Liquid chromatography method for determination of bivalirudin in human plasma and urine using automated ortho-phthalaldehyde derivatization and fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci, 2004;802(2):355-359. https://doi.org/10.1016/j.jchromb.2003.12.003
  13. Maraganore JM, Bourdon P, Jablonski J, Ramachandran KL, Fenton JW. 2nd. Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin. Biochemistry, 1990;29(30):7095-7101. https://doi.org/10.1021/bi00482a021
  14. Zhang X, Nieforth K, Lang JM, Rouzier-Panis R, Reynes J, Dorr A, Kolis S, Stiles MR, Kinchelow T, Patel IH. Pharmacokinetics of plasma enfuvirtide after subcutaneous administration to patients with human immunodeficiency virus: Inverse Gaussian density absorption and 2-compartment disposition. Clin Pharmacol Ther, 2002;72(1):10-19. https://doi.org/10.1067/mcp.2002.125945
  15. Douglas SA. Human urotensin-II as a novel cardiovascular target: 'heart' of the matter or simply a fishy 'tail'? Curr Opin Pharmacol, 2003;3(2):159-167. https://doi.org/10.1016/S1471-4892(03)00012-2
  16. John H, Walden M, Schafer S, Genz S, Forssmann WG. Analytical procedures for quantification of peptides in pharmaceutical research by liquid chromatography-mass spectrometry. Anal Bioanal Chem, 2004;378(4): 883-897. https://doi.org/10.1007/s00216-003-2298-y
  17. FDA. Bioanalytical Method Validation (Draft Guidance). Rockville, MD: Department of Health and Human Services, US Food and Drug Administration; 2013.