Rapid Quantitative Analysis of Vancomycin in Human Plasma and Urine Using LC-MS/MS

LC - MS/MS를 이용한 혈장과 뇨중에서 Vancomycin의 빠른정량분석

  • Kim, Hohyun (Department of Pharmacokinetics, Seoul Medical Science Institute (SCL)) ;
  • Roh, Hyeongjin (Department of Pharmacokinetics, Biocore. Co. Ltd.) ;
  • Han, Sang-Beom (Department of Pharmacokinetics, Seoul Medical Science Institute (SCL))
  • Received : 2002.05.08
  • Published : 2002.10.25

Abstract

In this study, a new quantitative analytical method has been developed for the rapid determination of vancomycin in human plasma and urine using liquid chromatography/tandem mass spectrometry (LC - MS/MS). Chromatography was carried out on a $C_{18}$ XTerra MS column ($2.1{\times}30mm$) with a particle size of $3.5{\mu}m$. The mobile phase was 0.25% formic acid in 10% acetonitrile and the flow rate was $250{\mu}L/min$. Vancomycin and caffeine (internal standard) were detected by MS/MS using multiple reaction monitoring (MRM). Vancomycin gives a predominant doubly protonated precursor molecule ($[M+2H]^{2+}$) at m/z 725.0 and a corresponding product ion of m/z 100.0. Detection of vancomycin was good, accurate and precise, with a limit of detection of 1 nM in plasma. The calibration curves for vancomycin in human plasma was linear in a concentration range of $0.01{\mu}M$ - $100{\mu}M$ for plasma. This method has been successfully applied to determine the concentration of vancomycin in human plasma and urine from pharmacokinetic study and relative studies.

본 연구에서는 LC - MS/MS를 이용해 혈장과 뇨중에서 반코마이신을 신속하게 정량분석하는 방법을 개발하였다. 크로마토그래피는 $C_{18}$ XTerra MS 컬럼 ($2.1{\times}30mm$, $3.5{\mu}m$)을 사용하여 분석하였다. 이동상으로는 0.25% 초산이 섞인 10% 아세토니트릴 용액을 사용하였으며, 유속은 $250{\mu}L/min$이다. 반코마이신과 카페인 (내부표준물질)은 multiple reaction monitoring (MRM) 방법을 사용하여 검출하였으며 반코마이신은 precursor ion m/z 725.0 ( $[M+2H]^{2+}$)와 product ion m/z 100.0을 사용하였다. 혈장에서 반코마이신의 검출한계는 1 nM이며 좋은 정확성과 정밀성을 보여주었다. 또한 혈장중에서 반코마이신의 정량범위는 $0.01{\mu}M$ - $100{\mu}M$이다. 혈장과 뇨중에서 반코마이신을 정량하는 이 분석방법은 약물동력학연구 및 관련연구에 성공적으로 적용되었다.

Keywords

References

  1. J. E. Geraci, Mayo Clin. Proc., 52, 631-634 (1977).
  2. R. E. VanScoy, S. N. Cohen, J. E. Geraci and J. A. Washington, Mayo Clin. Proc., 52, 216-219 (1977).
  3. J. E. Geraci and P. E. Hermans, Mayo Clin. Proc., 58, 88-91 (1983).
  4. P. E. Reynolds, Eur. J. Clin. Microbiol. Infect. Dis., 8, 943-950 (1989).
  5. R. Nagarajan, Glycopeptide Antibiotics, 63, ISBN 0-8247-9193 (1994).
  6. E. M. Tracy and s. DiTaranto, J. Pediatr. Oncol. Nurs., 19(2), 60-61 (2002).
  7. M. T. Suller and d. Lloyd, J. Appl. Microbiol., 92(5), 866-872 (2002).
  8. J. J. McAtee, S. L. Castle, Q. Jin and D. L. Boger, Bioorg. Med. Chem. Lett., 12(9), 1319-1322 (2002).
  9. D. W. Backes, H. I. Aboleneen and J. A. Simpson, J. Pharm. Biomed. Anal., 16, 1281-1287 (1998).
  10. J. Bauchet, E. Pussard and J. J. Garaud, J. Chromatogr., 414, 472-476 (1987).
  11. J. Luksa and A. Marusic, J. Chromatogr. B, 667, 277-281 (1995).
  12. P. Favetta, J. Guitton, N. bleyzac, C. Dufresne and J. Bureau, J. Chromatogr. B, 751, 377-382 (2001).
  13. B. Robredo, K. V. Singh, F. Baquero, B.E. Murray and C. Torres, J. Food Microbiol., 54(3), 197-204 (2000).
  14. R. Lorenz, M. Herrmann, A. M. Kassem, N. Lehn, H. Neuhaus and M. Classen, Endoscopy, 30(8), 708-712 (1998).
  15. A. L. Somerville, D. H. wright and J. C. Rotschafer, Pharmacotherapy, 19(6), 702-707 (1999).
  16. L. M. Perino and B. A. Mueller, Ann Pharmacother., 27(7-8), 892-893 (1993).
  17. D. Farin, G. A. Piva, I. Gozlan and R. Kitzes-Cohen, J. Pharm. Biomed. Anal., 18(3), 367-372 (1998).
  18. L. O. White, H. A. Holt, D. S. Reeves and A. P. MacGowan, J. Antimicrob. Chemother., 39(3), 355-361 (1997).
  19. H. Hosotsubo, J. Chromatogr., 487(2), 421-427 (1989).