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 |
| |
Authors: | David Guillén Frederic Cofán Emilio Ros Olga Millán Montse Cofán Antoni Rimola and Mercè Brunet |
| |
Institution: | (1) Pharmacology and Toxicology Laboratory (CDB), IDIBAPS, Hospital Clinic of Barcelona, Barcelona University, C/Villarroel 170, 08036 Barcelona, Spain;(2) Centro de Investigaci?n Biom?dica en Red de Enfermedades Hep?ticas y Digestivas (CiberEHD), 08036 Barcelona, Spain;(3) Renal Transplant Unit, Hospital Clinic, IDIBAPS, Hospital Clinic of Barcelona, Barcelona University, 08036 Barcelona, Spain;(4) Lipid Clinic, Endocrinology and Nutrition Services, IDIBAPS and Ciber Fisiopatolog?a de la Obesidad y Nutrici?n (CiberEHD), Hospital Clinic of Barcelona, Barcelona University, 08036 Barcelona, Spain |
| |
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. |
| |
Keywords: | Atorvastatin Ortho-hydroxyatorvastatin Mass spectrometry Liquid chromatography Solid-phase extraction Kidney transplanted recipients |
本文献已被 SpringerLink 等数据库收录! |
|