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

作者：Guillen David; Cofan Frederic; Ros Emilio; Millan Olga; Cofan Montse; Rimola Antoni; Brunet Merce^*

来源：Analytical and Bioanalytical Chemistry, 2009, 394(6): 1687-1696.

DOI：10.1007/s00216-009-2852-3

• Atorvastatin
• Ortho-hydroxyatorvastatin
• Mass spectrometry
• Liquid chromatography
• Solid-phase extraction
• Kidney transplanted recipients

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.

• 出版日期2009-7