title: Ultra high performance liquid chromatography tandem mass spectrometric detection in clinical analysis of simvastatin and atorvastatin.
abstract: Simvastatin and atorvastatin belong to the group of hypolipidemic drugs, more exactly to the second generation of inhibitors of microsomal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. They induce a significant reduction in total cholesterol, low-density lipoprotein cholesterol and plasma triglycerides, therefore they are widely used in the treatment of hypercholesterolemia even of its severe form-familiar hypercholesterolemia. Simvastatin and atorvastatin as the most widely used statins in clinical treatment and their hydroxy-acid/lactone forms were determined by means of UPLC in connection with triple quadrupole mass spectrometer. Deuterium labeled reference standard compounds were used as internal standards for the quantitation. Separation was performed on Acquity BEH C18 (100 mm x 2.1 mm, 1.7 microm) using gradient elution by mobile phase containing acetonitrile and ammonium acetate pH 4.0, which is convenient in order to prevent interconversion of analytes. ESI in positive mode was used for the ionization of all compounds. Two SRM (selected reaction monitoring) transitions were carefully optimized for each analyte in order to get high sensitivity and selectivity. SPE on Discovery DSC-18 was used as a sample preparation step. Intra-day precision was generally within 10% RSD, while inter-day precision within 15% RSD. Method accuracy expressed as recovery ranged from 75 to 100%. The method was validated with the sensitivity reaching LOQ 0.08-5.46 nmol/l and LOD 0.01-1.80 nmol/l in biological samples. Atorvastatin, simvastatin, its metabolites and hydroxy-acid/lactone forms were monitored in human serum and in lipoprotein fractions (LDL, HDL and VLDL) at patients with end stage renal diseases.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. nol@email.cz
authors.forename: Lucie
authors.initials: L
authors.lastname: Nováková
authors.forename: Hana
authors.initials: H
authors.lastname: Vlcková
authors.forename: Dalibor
authors.initials: D
authors.lastname: Satínský
authors.forename: Petr
authors.initials: P
authors.lastname: Sadílek
authors.forename: Dagmar
authors.initials: D
authors.lastname: Solichová
authors.forename: Milan
authors.initials: M
authors.lastname: Bláha
authors.forename: Vladimír
authors.initials: V
authors.lastname: Bláha
authors.forename: Petr
authors.initials: P
authors.lastname: Solich
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000097:blood* / Q000627:therapeutic use; D000069059:Atorvastatin; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006538:Heptanoic Acids / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000097:blood* / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D019821:Simvastatin / Q000097:blood* / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin