LC-MS/MS method for the determination of several drugs used in combined cardiovascular therapy in human plasma.
A simple, fast and validated method is reported for the simultaneous analysis, in human plasma, of several drugs usually combined in cardiovascular therapy (atenolol, bisoprolol, hydrochlorothiazide, chlorthalidone, salicylic acid, enalapril and its active metabolite enalaprilat, valsartan and fluvastatin) using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI), working in multiple reaction monitoring mode (MRM). Separation of analytes and internal standard (pravastatin) was performed on a Luna C18(2) (150mm×4.6mm, 3μm) column using a gradient elution mode with a run time of 15min. The mobile phase consisted of a mixture of acetonitrile and water containing 0.01% formic acid and 10mM ammonium formate at pH 4.1. Sample treatment consisted of a simple protein precipitation with acetonitrile, enabling a fast analysis. The method showed good linearity, precision (RSD% values between 0.7% and 12.7%) and accuracy (relative error values between 0.9% and 14.0%). Recoveries were within 68-106% range and the ion-suppression was not higher than 22% for any analyte. The method was successfully applied to plasma samples obtained from patients under combined cardiovascular treatment.
Gonzalez
Oskar
O
Analytical Chemistry Department, Science and Technology Faculty, Basque Country University/EHU, P.O. Box 644, 48080 Bilbao, Basque Country, Spain.
Iriarte
Gorka
G
Rico
Estitxu
E
Ferreirós
Nerea
N
Maguregui
Miren Itxaso
MI
Alonso
Rosa Maria
RM
Jiménez
Rosa Maria
RM
D000645:Ammonium Sulfate / Q000737:chemistry; D001262:Atenolol / Q000097:blood*; D017298:Bisoprolol / Q000097:blood*; D002317:Cardiovascular Agents / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005561:Formates / Q000737:chemistry; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D002317:Cardiovascular Agents; D005561:Formates; C030544:formic acid; D001262:Atenolol; D000645:Ammonium Sulfate; D017298:Bisoprolol