, Volume 57, Issue 1–2, pp 23–27 | Cite as

Development and validation of a direct plasma injection LC-MS method for YM087 and YM440 and metabolites in human plasma

  • J. van Zijtveld
  • S. van den Berg
  • P. Swart
Originals Column Liquid Chromatography


A fully automated, direct plasma-injection technique using an LC coupled to a quadrupole mass spectrometric detector with an on-line, sample clean-up procedure for two new pharmaceutical products, YM087 and YM440, has been developed.

Plasma samples containing YM440 were mixed with internal standard or plasma containing YM087 and were injected into a chromatographic system based on two coupled columns. An extraction column packed with alkyl-diol-silica (ADS) was used for online sample cleanup. Using a back-flush technique analytes were subsequently transferred to an analytical column, for separation. Detection was based on tandem mass spectrometry either in electronspray or in APCI mode. Despite the relatively small volumes of plasma injected, reasonably low limits of quantitation were achieved. Validation of both assays was performed using guidelines concerning method validation. All parameters studied were within acceptance criteria. The methods were successfully applied to clinical pharmacokinetic studies.

Key Words

Column liquid chromatography LC-MS-MS Direct plasma injection, ADS Mass spectrometry detection Drugs and metabolites 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    van Zijtveld, J.; van Hoogdalem, E.J.J. Chromatogr. B. 1999 726, 169–174.Google Scholar
  2. [2]
    Boos, K.S.; Rudolphi, A.; Vielhauer, S.; Walfort, A.; Lubda, D.; Eisenbeiss, F.,Fresenius J. Anal. Chem. 1995, 352 684–690.CrossRefGoogle Scholar
  3. [3]
    Vielhauer, S.; Rudolphi, A.; Boos, K.S.; Siedel, D.J. Chromatogr. 1995, 666 315–322.Google Scholar
  4. [4]
    Rudolphi, A.; Vielhauer, S.; Boos, K.S.; Siedel, D.; Bathge, J.M.; Berger, H.J. Phar. Biomed. Anal. 1995, 13, 615–623.CrossRefGoogle Scholar
  5. [5]
    Rudolphi, A.; Boos, K.S.HPLC 1995, Innsbruck,1995.Google Scholar
  6. [6]
    Boos, K.S.; Grimm, C.H.Trends in Analytical Chemistry,1999,18, 175–180.CrossRefGoogle Scholar
  7. [7]
    Massart, D.L.; Van de Ginste, B.G.; Deming, S.N.; Michotte, Y.; Kaufman, I.Chemometrics, A textbook, Chapters 5 and 9, Elsevier Amsterdam,1988.Google Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 2003

Authors and Affiliations

  • J. van Zijtveld
    • 1
  • S. van den Berg
    • 1
  • P. Swart
    • 1
  1. 1.Biological Development DepartmentYamanouchi Europe B.V.LeiderdorpThe Netherlands

Personalised recommendations