, Volume 52, Supplement 1, pp S113–S119 | Cite as

Development of an analytical methodology from toxicokinetic to clinical studies for the anti-migraine drug frovatriptan

  • L. Laugher
  • R. Briggs
  • J. Doughty
  • T. A. G. Noctor
Particular Analytes


To support the development programme of the anti-migraine drug, frovatriptan, an analytical method using HLPC-UV was validated in rat blood and subsequently cross-validated in dog and mouse blood to analyse samples generated from pre-clinical studies. The method was also evaluated in rabbit blood, however the method proved insufficiently selective/specific for this particular matrix. A need for a more sensitive method suitable for the analysis of a large number of samples to support clinical studies was identified. Advances in analytical technology over this period of development led to the development of LC-MS-MS analytical methods for human and rabbit whole blood that were appropriate, for the changing requirements of each study. A summary of the respective validation data, together with a discussion on the validation procedures employed, has been presented.

Key Words

Column liquid chromatography LC-MS/MS Validation Frovatriptan Anti-migraine drug 


  1. [1]
    Goldstein, M.E.; Chen, T.C.;Adv. Neurol. 1982,33, S-377–S-390.Google Scholar
  2. [2]
    Parsons, A.A.; Parker, S.G.; Raval, P.; Campbell, C.A.; Lewis, V.A.; Griffiths, R.; Hunter, A.J.; Hamilton, T.C.; King, F.D.J. Cardiovasc. Pharmacol. 1997,30, S-136–S-141.CrossRefGoogle Scholar
  3. [3]
    Hill, H.M.; Tennant, K.; Noctor, T.A.G.; Pratt, S. inBiofluid Assay for Peptide-Related and Other Drugs, Reid, E.; Hill, H.M.; Wilson, I.D., (Eds.),Royal Society of Chemistry, Cambridge, UK,1996,24, S-223–S-224.Google Scholar
  4. [4]
    Dadgar, D.; Burnett, P.E.; Choc, M.G.; Gallicano, K.; Hooper, J.W.J. Pharm. and Biomed. Anal. 1995,13 (2), S-89–S-97.Google Scholar
  5. [5]
    Shah, V.P.; Midha, K.K.; Dighe, S.; MCGiveray, I.J.; Skelly, J.P.; Yacobi, A.; Layloff, T.; Vishwanathan, C.T.; Cook, C.E.; McDowall, R.D.; Pittman, K.A.; Spector, S.Pharm. Res. 1992,9, S-588–-S592.Google Scholar
  6. [6]
    Toxicokinetics: A Guidance for Assessing Systemic Exposure in Toxicology Studies, ICH (International Conference on Harmonisation) Topic S3A, CPMP/ICH/384/95, The European Agency for the Evaluation of Medicinal Products1995.Google Scholar
  7. [7]
    Food and Drug Administration Reviewer Guidance, Validation of Chromatographic Methods, CDER. Washington D.C.,1994.Google Scholar
  8. [8]
    Bentley, M.; Borlak, J.; Tennant, K. inBiofluid Assay for Peptide Related and Other Drugs, Reid, E.; Hill, H.M.; Wilson, I.D., Eds.ESC 1996,24, S-327–S-328.Google Scholar
  9. [9]
    Guidance for Industry, Bioanalytical Methods Validation for Human Studies, CDER1998.Google Scholar
  10. [10]
    Hill, H.M.Chromatographia 2000,52 (Suppl.) S-65–S-69.Google Scholar
  11. [11]
    Muirhead, D.C.; Smart, T.S.Chromatographia 2000,52 (Suppl.) S-72–S-75.Google Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 2000

Authors and Affiliations

  • L. Laugher
    • 1
  • R. Briggs
    • 2
  • J. Doughty
    • 3
  • T. A. G. Noctor
    • 4
  1. 1.Department of Biopharmaceutical AnalysisCovance LaboratoriesHarrogateUK
  2. 2.Vernalis LimitedGuildfordUK
  3. 3.Covance Clinical Research UnitProject Management GroupLeedsUK
  4. 4.York Bioanalytical Solutions Limited, Genesis TwoYork University Science ParkHeslingtonUK

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