TITLE

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

AUTHOR(S)
Guillén, David; Cofán, Frederic; Ros, Emilio; Millán, Olga; Cofán, Montse; Rimola, Antoni; Brunet, Mercè
PUB. DATE
July 2009
SOURCE
Analytical & Bioanalytical Chemistry;Jul2009, Vol. 394 Issue 6, p1687
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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.
ACCESSION #
42211568

 

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