Analytical and Bioanalytical Chemistry

, Volume 386, Issue 2, pp 275–285 | Cite as

Validated HPLC–MS–MS method for simultaneous determination of atorvastatin and 2-hydroxyatorvastatin in human plasma—pharmacokinetic study

  • V. Bořek-Dohalský
  • J. Huclová
  • B. Barrett
  • B. Němec
  • I. Ulč
  • I. Jelínek
Original Paper

Abstract

Cholesterol-reducing statin drugs are the most frequently prescribed agents for reducing morbidity and mortality related to coronary heart disease. In this publication a validated, highly sensitive, and selective isocratic HPLC method is reported for quantitative determination of the major statin drug atorvastatin (ATV) and its metabolite 2-hydroxyatorvastatin (HATV). Detection was performed with an electrospray ionization triple-quadrupole mass spectrometer equipped with an ESI interface operating in positive-ionization mode. Multiple reaction monitoring (MRM) was used for MS–MS detection. The calibration plot was linear in the concentration range 0.10–40.00 ng mL−1 for both ATV and HATV. Inter-day and intra-day precision and accuracy of the proposed method were characterized by measurement of relative standard deviation (RSD) and percentage deviation, respectively; both were less than 8% for both analytes. The limit of quantitation was 0.02 ng mL−1 for ATV and 0.07 ng mL−1 for HATV. The method was used for pharmacokinetic study of ATV and HATV. Pharmacokinetic data for all analytes are also reported.

Keywords

Atorvastatin HPLC MS Plasma Pharmacokinetic study 

References

  1. 1.
    Lipitor Tablets, 10 mg, 20 mg, 40 mg, Summary of Product Characteristics, Parke–Davis, UK, October 2002Google Scholar
  2. 2.
    Sortis 10 mg, 20 mg, 40 mg, Souhrn údaj o přípravku (Summary of product characteristics in Czech), Parke– Davis, Germany, February 5, 2003Google Scholar
  3. 3.
    Lea AP, McTavish D (1997) Drugs 53:828–847CrossRefGoogle Scholar
  4. 4.
    Kantola T, Kivistö KT, Neuvonen PJ (1998) Clin Pharmacol Ther 64:58–65CrossRefGoogle Scholar
  5. 5.
    Lilja JJ, Kivistö KT, Neuvonen PJ (1999) Clin Pharmacol Ther 66:118–127Google Scholar
  6. 6.
    Ertuk S, Aktas ES, Ersoy L, Ficicioglu S (2003) J Pharm Biomed Anal 33:1017–1023CrossRefGoogle Scholar
  7. 7.
    Erk N (2004) Crit Rev Anal Chem 34:1–7CrossRefGoogle Scholar
  8. 8.
    van Pelt CK, Corso TN, Schltz GA, Lowes S, Henion J (2001) Anal Chem 73:582–588CrossRefGoogle Scholar
  9. 9.
    Jemal M, Ouyang Z, Chen BC, Teitz D (1999) Rapid Commun Mass Spectrom 13:1003–1015CrossRefGoogle Scholar
  10. 10.
    Bullen WW, Miller RA, Hayes RN (1999) J Am Soc Mass Spectrom 10:55–66CrossRefGoogle Scholar
  11. 11.
    Posvar EL, Radulovic LL, Cilla DD, Whitfield LR, Sedman AJ (1996) J Clin Pharmacol 36:728–731Google Scholar
  12. 12.
    Radulovic LL, Cilla DD, Posvar EL, Sedman AJ, Whitfield LR (1995) J Clin Pharmacol 35:990–994Google Scholar
  13. 13.
    Atorvastatin Calcium, PDR for Lipitor Tablets, Pfizer Pharmaceuticals, November 2002. Available at: http://www.drugs.com/pdr/atorvastatin_calcium.html. Accessed: June 14, 2005

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • V. Bořek-Dohalský
    • 1
  • J. Huclová
    • 1
  • B. Barrett
    • 1
  • B. Němec
    • 1
  • I. Ulč
    • 1
  • I. Jelínek
    • 2
  1. 1.Bioanalytical LaboratoryCEPHA s.r.o. PlzenPlzenCzech Republic
  2. 2.Department of Analytical ChemistryCharles University PraguePraha 2Czech Republic

Personalised recommendations