title: Development of an LC-MS/MS method for the quantitation of 55 compounds prescribed in combined cardiovascular therapy.
abstract: This paper reports an LC-MS/MS method with positive electrospray ionization for the screening of commonly prescribed cardiovascular drugs in human plasma, including compounds with antihypertensive (57), antidiabetic (12), hypolipemiant (5), anticoagulant (2) and platelet anti-aggregation (2) effects. Sample treatment consisted of a simple protein precipitation with MeOH/0.1 M ZnSO₄ (4:1, v/v) solution after the addition of internal standard, followed by evaporation and reconstitution. Analytes separation was performed on a Polar-RP column (150 m x 2 mm, 4 μm) using a gradient elution of 15 min. The MS system was operated in MRM mode, monitoring one quantitation and one confirmation transition for each analyte. The recovery of the protein precipitation step ranged from 50 to 70% for most of the compounds, while some were considerably affected by matrix effects. Since several analytes fulfilled the linearity, accuracy and precision values required by the ICH guidelines, the method proved to be suitable for their quantitative analysis. The limits of quantitation varied from 0.38 to 9.1 μg/L and the limits of detection from 0.12 to 5.34 μg/L. The method showed to be suitable for the detection of plasma samples of patients under cardiovascular treatment with the studied drugs, and for 55 compounds reliable quantitative results could be obtained.
authors.affiliation: Analytical Chemistry Department, Science and Technology Faculty Leioa, Spain.
authors.forename: Oskar
authors.initials: O
authors.lastname: Gonzalez
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Alonso
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreirós
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weinmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dresen
mesh_terms: D002317:Cardiovascular Agents / Q000097:blood*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002853:Chromatography, Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D006401:Hematologic Agents / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood; D000960:Hypolipidemic Agents / Q000097:blood; D016018:Least-Squares Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002317:Cardiovascular Agents; D006401:Hematologic Agents; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents