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Determination of atorvastatin and its metabolite ortho-hydroxyatorvastatin in human plasma by on-line anion-exchange solid-phase extraction and liquid chromatography tandem mass spectrometry

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Abstract

A rapid, sensitive, and specific method was developed and validated using liquid chromatography-tandem mass spectrometry for the simultaneous quantitation of atorvastatin (ATV) and its major metabolite ortho-hydroxyatorvastatin (o-HATV) in human plasma. The sample preparation involved a liquid–liquid extraction without chlorinated solvents and an on-line solid-phase extraction exploring the possibilities that anion exchange offers. The analytical method presented intraday and day-to-day variation below 10%; intraday and day-to-day accuracy stood between 94% and 105%; the limit of quantification was 0.1 ng/mL for ATV and 0.5 ng/mL for o-HATV; and the recovery was above 75% for both molecules. This method was applied successfully to quantitate ATV and o-HATV concentrations in an unstudied renal transplant recipient cohort treated with an immunosuppressive regime of tacrolimus and mycophenolic acid and a cohort of hypercholesterolemic patients included in the study as a control group. It can be used to evaluate patient adherence, drug–drug interactions, and pharmacokinetic/pharmacodynamic relationships. The results in our study showed that ATV and o-HATV levels in the renal transplant group were significantly increased (p < 0.001), compared to the hypercholesterolemic group.

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Acknowledgments

We would like to thank Pfizer, Groton, USA for donating ATV, o-HATV and pHATV. CiberEHD and CiberOBN are funded by the Instituto de Salud Carlos III.

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Authors and Affiliations

  1. Pharmacology and Toxicology Laboratory (CDB), IDIBAPS, Hospital Clinic of Barcelona, Barcelona University, C/Villarroel 170, 08036, Barcelona, Spain

    David Guillén, Olga Millán & Mercè Brunet

  2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiberEHD), 08036, Barcelona, Spain

    Olga Millán, Antoni Rimola & Mercè Brunet

  3. Renal Transplant Unit, Hospital Clinic, IDIBAPS, Hospital Clinic of Barcelona, Barcelona University, 08036, Barcelona, Spain

    Frederic Cofán

  4. Lipid Clinic, Endocrinology and Nutrition Services, IDIBAPS and Ciber Fisiopatología de la Obesidad y Nutrición (CiberEHD), Hospital Clinic of Barcelona, Barcelona University, 08036, Barcelona, Spain

    Emilio Ros & Montse Cofán

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  1. David Guillén
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  2. Frederic Cofán
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  3. Emilio Ros
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  4. Olga Millán
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  5. Montse Cofán
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  7. Mercè Brunet
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Correspondence to Mercè Brunet.

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Guillén, D., Cofán, F., Ros, E. et al. Determination of atorvastatin and its metabolite ortho-hydroxyatorvastatin in human plasma by on-line anion-exchange solid-phase extraction and liquid chromatography tandem mass spectrometry. Anal Bioanal Chem 394, 1687–1696 (2009). https://doi.org/10.1007/s00216-009-2852-3

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  • DOI: https://doi.org/10.1007/s00216-009-2852-3

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