, Volume 60, Issue 7–8, pp 391–397 | Cite as

Systematic Selection of Internal Standard with Similar Chemical and UV Properties to Drug to Be Quantified in Serum Samples



This paper describes the selection of an internal standard for the quantification of a model drug in blood samples by a predictive approach based on three retention models for ionizable compounds. The three models are the Abraham’s solvation parameter, simple and improved Log(P) models (P is the partition coefficient between 1-octanol and water). The separation is performed by a Zorbax StableBond ODS column, and acetonitril-(ACN)/water mobile phase (0.1% trifluoroacetic acid, TFA) via a linear gradient elution. The retention times of reference solutes are obtained under the separation conditions, and correlated with their molecular descriptors via linear and nonlinear regression to obtain the model equations for the internal standard prediction. The models are then used to compute the retention of internal standard candidates that possess very similar UV and physical properties to the drug. The final internal standard is chosen by not only the desired retention time, but also the UV and partition properties for the ideal recovery and detection. 4-aminoacetophenone was finally selected as the internal standard for the quantification.


Column liquid chromatography Ion-pair chromatography Solvation parameter model Retention prediction Log (P) model 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



The authors would like to sincerely acknowledge the support of department of Transdermal Drug Delivery, 3M Drug Delivery Systems Division, 3M Company, for this study.


  1. Li J (2001) J Chromatogr (A) 927:19–30Google Scholar
  2. Li J, Shah DS (2002) J Chromatogr (A) 954:159–171Google Scholar
  3. Li J (2001) J Chromatogr (A) 982:209–223Google Scholar
  4. Li J (2004) Anal Chim Acta 522:113–126CrossRefGoogle Scholar
  5. Li J (2004) Chromatographia 60:63–71CrossRefGoogle Scholar
  6. Abraham MH, Chadha HS, Martins F, Mitchell RC, Bradbury MW, Gratton JA (1999) Pestic Sci 55:78–88CrossRefGoogle Scholar
  7. Abraham MH, Chadha HS (1996) Application of a salvation equation to drug transport properties. In: Pliska V, Testar B, Vanda Waterbeemed H (eds) Lipophilicity in drug action and toxicology. VCH Press, Weinheim pp. 311–337Google Scholar
  8. Abraham MH, Ibrahim, A, Zissimos AM (2004) J Chromatogr (A) 1037:29–47Google Scholar
  9. Miyake K, Terada H (1982) J Chromatogr (A) 240:9–20Google Scholar
  10. Miyake K, Kitaura F, Mizuno N, Terada H (1987) J Chromatogr (A) 389:47–56Google Scholar
  11. Miyake K, Kitaura F, Mizuno N (1988) J Chromatogr (A) 439:227–235Google Scholar
  12. Miyake K, Kitaura F, Mizuno N (1986) Chem Pharm Bull 34:4787–4796Google Scholar
  13. Cai B, Li J (1999) Anal Chim Acta, 399:249–258Google Scholar
  14. Petritis KN, Chaimbault P, Elfakir C, Dreux M (1999) J Chromatogr (A) 833:147–155Google Scholar
  15. Patthy MJ (1992) J Chromatogr 592:143–156CrossRefGoogle Scholar
  16. Patthy MJ (1994) J Chromatogr (A) 660 (1994) 17–23Google Scholar
  17. Patthy M, Gyenge R (1988) J Chromatogr 449:191–205CrossRefPubMedGoogle Scholar
  18. Guo D, Mant CT, Hodges RS (1987) J Chromatogr 386:205–222CrossRefPubMedGoogle Scholar
  19. Bennett HPJ, Browne CA, Solomon S (1980) J Liq Chromatogr 3:1353–1365Google Scholar
  20. Mannhold R, Petrauskas A (2003) QSAR Comb Sci 22:466–475Google Scholar
  21. Depot M, Leroux S, Caille G (1997) J Chromatogr (B) 693:399–406Google Scholar
  22. Bauer S, Stormer E, Kaiser R, Tremblay P, Brockmoller J, Roots I (2002) Biomed Chromatogr 16:187–190CrossRefPubMedGoogle Scholar
  23. Grasselli JG (1973) Atlas of spectral data and physical constants for organic compounds, CRC Press, Cleveland, Section B, p. B91Google Scholar
  24. Abraham MH, Chada HS, Whiting GS, Mitchel RC (1994) J Pharm Sci 83:1085–1100PubMedGoogle Scholar
  25. Dean JA (1999) Handbook of chemistry, 5th Ed., McGraw-Hill, NY, p 8.24–8.72Google Scholar

Copyright information

© Friedr. Vieweg&Sohn/GWV Fachverlage GmbH 2004

Authors and Affiliations

  1. 1.Transdermal Drug Delivery, 3M Drug Delivery Systems, 3M CenterSt. PaulUSA

Personalised recommendations