title: Validated HPLC-MS-MS method for simultaneous determination of atorvastatin and 2-hydroxyatorvastatin in human plasma-pharmacokinetic study.
abstract: Cholesterol-reducing statin drugs are the most frequently prescribed agents for reducing morbidity and mortality related to coronary heart disease. In this publication a validated, highly sensitive, and selective isocratic HPLC method is reported for quantitative determination of the major statin drug atorvastatin (ATV) and its metabolite 2-hydroxyatorvastatin (HATV). Detection was performed with an electrospray ionization triple-quadrupole mass spectrometer equipped with an ESI interface operating in positive-ionization mode. Multiple reaction monitoring (MRM) was used for MS-MS detection. The calibration plot was linear in the concentration range 0.10-40.00 ng mL(-1) for both ATV and HATV. Inter-day and intra-day precision and accuracy of the proposed method were characterized by measurement of relative standard deviation (RSD) and percentage deviation, respectively; both were less than 8% for both analytes. The limit of quantitation was 0.02 ng mL(-1) for ATV and 0.07 ng mL(-1) for HATV. The method was used for pharmacokinetic study of ATV and HATV. Pharmacokinetic data for all analytes are also reported.
authors.affiliation: Bioanalytical Laboratory, CEPHA s.r.o. Plzen, Komenskeho 19, 32300 Plzen, Czech Republic. dohalsky@cepha.cz
authors.forename: V
authors.initials: V
authors.lastname: Borek-Dohalský
authors.forename: J
authors.initials: J
authors.lastname: Huclová
authors.forename: B
authors.initials: B
authors.lastname: Barrett
authors.forename: B
authors.initials: B
authors.lastname: Nemec
authors.forename: I
authors.initials: I
authors.lastname: Ulc
authors.forename: I
authors.initials: I
authors.lastname: Jelínek
mesh_terms: D000924:Anticholesteremic Agents / Q000097:blood* / Q000493:pharmacokinetics; D000069059:Atorvastatin / Q000031:analogs & derivatives; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006538:Heptanoic Acids / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D011758:Pyrroles / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: C518963:2-hydroxyatorvastatin; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin