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-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.
Guillén
David
D
Pharmacology and Toxicology Laboratory (CDB), IDIBAPS, Hospital Clinic of Barcelona, Barcelona University, C/Villarroel 170, 08036 Barcelona, Spain. davidguillentunica@hotmail.com
Cofán
Frederic
F
Ros
Emilio
E
Millán
Olga
O
Cofán
Montse
M
Rimola
Antoni
A
Brunet
Mercè
M
D000328:Adult; D000368:Aged; D000838:Anions / Q000737:chemistry*; D000069059:Atorvastatin / Q000031:analogs & derivatives; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006538:Heptanoic Acids / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009862:Online Systems; D011758:Pyrroles / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
C518963:2-hydroxyatorvastatin; D000838:Anions; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin