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  • 1 University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia
  • 2 University of Belgrade, Studentski trg 12–16, Belgrade, Serbia
  • 3 University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia

A simple and sensitive liquid chromatography—tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C18 Analytical, 4.6 × 100 mm (3.5 μm) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 μL min−1. The column was kept at constant temperature (25 °C), and autosampler tray temperature was set at 4 °C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 → Q3, collision energy) atorvastatin (559.47 → 440.03, 22 eV), atorvastatin lactone (541.36 → 448.02, 19 eV), ortho-ohydroxyatorvastatin (575.20 → 440.18, 20 eV), para-hydroxyatorvastatin (575.54 → 440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5–20 ng mL−1 for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1–20 ng mL−1 for atorvastatin and atorvastatin lactone with excellent linearity (r2 ≥ 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL−1 for orth-ohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL−1 for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.

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  • [1]

    C. D. Mathers , D. Ma Fat, M. Inoue, C. Rao, and A. D. Lopez, Bull. W. H. O., 83, 171177 (2005)

  • [2]

    R. S. Rosenson Atherosclerosis, 173, 112 (2004)

  • [3]

    G. Paragh , D. Törocsik, I. Seres, M. Harangi, L. Illyés, Z. Balogh, and P. Kovács, Curr. Med. Res. Opin., 20(8), 13211327 (2004)

  • [4]

    A. Nagila , T. Permpongpaiboon, S. Tantrarongroj, P. Porapakkham, K. Chinwattana, S. Deakin, and S. Porntadavity, Pharmacol. Rep., 61, 892898 (2009)

    • Search Google Scholar
    • Export Citation
  • [5]

    F. Taylor , M. D. Huffman, A. F. Macedo, T. H. M. Moore, M. Burke, G. D. Smith, K. Ward, and S. Ebrahim, BMJ, 348, g280 (2014)

  • [6]

    P. H. Chong , J. D. Seeger, and C. Frankin, Am. J. Med., 111, 390400 (2001)

  • [7]

    W. Jacobsen , B. Kuhn, A. Soldner, G. Kirchner, K. F. Sewing, P. A. Kollman, L. Z. Benet, and U. Christians, Drug Metab. Dispos., 28, 13691378 (2000)

    • Search Google Scholar
    • Export Citation
  • [8]

    Parke-Davis, Product information: Lipitor (Atorvastatin Calcium), Parke-Davis (Division of Pfizer Inc.), Ann Arbor, MI, USA, 2004

  • [9]

    R. J. Valesky , L. Liu, D. G. Musson, and J. J. Zhao, J. Pharmacol. Toxicol. Methods, 57, 6169 (2008)

  • [10]

    E. L. Posvar , L. L. Radulovic, D. D. Cilla, L. R. Whitfield, and A. J. Sedman, J. Clin. Pharmacol., 36, 728731 (1996)

  • [11]

    N. Erk , Crit. Rev. Anal. Chem., 34, 17 (2004)

  • [12]

    T. G. Altuntas and N. Erk, J. Liq. Chromatogr. Related Technol., 27, 8393 (2004)

  • [13]

    G. Bahrami , B. Mohammadi, S. Mirzaeei, and A. Kiani, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci., 826, 4145 (2005)

  • [14]

    H. R. Shen , Z. D. Li, and M. K. Zhong, Pharmazie, 61, 1820, 2006

  • [15]

    A. Zarghi , A. Shafaati, S. M. Foroutan, and A. Khoddam, Arzneimittelforschung, 55, 451454 (2005)

  • [16]

    C. K. Van Pelt , T. N. Corso, G. A. Schultz, S. Lowes, and J. Henion, Anal. Chem., 73, 582588 (2001)

  • [17]

    S. Miao and C. D. Metcalfe, J. Mass. Spectrom., 38, 2734 (2003)

  • [18]

    V. Borek-Dohalsky , J. Huclova, B. Barrett, B. Nemec, I. Ulc, and I. Jelinek, Anal. Bioanal. Chem., 386, 275285 (2006)

  • [19]

    W. W. Bullen , R. A. Miller, and R. N. Hayes, J. Am. Soc. Mass. Spectrom., 10, 5566 (1999)

  • [20]

    D. Guillen , F. Cofan, E. Ros, O. Millan, M. Cofan, A. Rimola, and M. Brunet, Anal. Bioanal. Chem., 394, 16871696 (2009)

  • [21]

    M. Hermann , H. Christensen, and J. L. Reubsaet, Anal. Bioanal. Chem., 382, 12421249 (2005)

  • [22]

    M. Jemal , Z. Ouyang, B. C. Chen, and D. Teitz, Rapid Commun. Mass. Spectrom., 13, 10031015 (1999)

  • [23]

    D. Liu , J. Jiang, H. Zhou, and P. Hu, J. Chromatogr. Sci., 46, 862866 (2008)

  • [24]

    L. Ma , J. Dong, X. J. Chen, and G. J. Wang, Chromatographia, 65, 737741 (2007)

  • [25]

    R. V. Nirogi , V. N. Kandikere, M. Shukla, K. Mudigonda, S. Maurya, R. Boosi, and Y. Anjaneyulu, Biomed. Chromatogr., 20, 924936 (2008)

  • [26]

    J. S. Macwan , I. A. Ionita, M. Dostalek, and F. Akhlaghi, Anal. Bioanal. Chem., 400, 423433 (2011)

  • [27]

    P. Partani , S. M. Verma, S. Gurule, A. Khuroo, and T. Monif, J. Pharm. Anal., 4(1), 2636 (2014)

  • [28]

    European Medicines Agency, Guideline on Bioanalytical Method Validation, Committee for Medicinal Products for Human Use, 2011

  • [29]

    Guidance for Industry, Bioanalytical Method Validation, Food and Drug Administration, 2001

  • [30]

    M. Jemal and Y. O. Xia, J. Pharm. Biomed., 22, 813827 (2000)

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