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

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-liqui...

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Veröffentlicht in:Analytical and bioanalytical chemistry 2009-07, Vol.394 (6), p.1687-1696
Hauptverfasser: Guillén, David, Cofán, Frederic, Ros, Emilio, Millán, Olga, Cofán, Montse, Rimola, Antoni, Brunet, Mercè
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container_issue 6
container_start_page 1687
container_title Analytical and bioanalytical chemistry
container_volume 394
creator Guillén, David
Cofán, Frederic
Ros, Emilio
Millán, Olga
Cofán, Montse
Rimola, Antoni
Brunet, Mercè
description 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.
doi_str_mv 10.1007/s00216-009-2852-3
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source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Adult
Aged
All terrain vehicles
Analytical Chemistry
Anions - chemistry
Atorvastatin Calcium
Biochemistry
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Chromatographic methods and physical methods associated with chromatography
Chromatography, Liquid - methods
Exact sciences and technology
Extraction
Female
Food Science
Heptanoic Acids - blood
Heptanoic Acids - chemistry
Heptanoic Acids - metabolism
Human
Humans
Laboratory Medicine
Male
Mass spectrometry
Mathematical analysis
Metabolites
Middle Aged
Monitoring/Environmental Analysis
On-line systems
Online Systems
Original Paper
Other chromatographic methods
Pyrroles - blood
Pyrroles - chemistry
Pyrroles - metabolism
Solid Phase Extraction - methods
Spectrometric and optical methods
Tandem Mass Spectrometry - methods
Transplants
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
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