Liquid chromatography/negative ion electrospray tandem mass spectrometry method for the quantification of fluvastatin in human plasma: validation and its application to pharmacokinetic studies

Abstract

A simple, sensitive and rapid high-performance liquid chromatography/negative ion electrospray tandem mass spectrometry method was developed and validated for the assay of fluvastatin in human plasma. Following solid-phase extraction, the analytes were separated using an isocratic mobile phase on a reversed-phase column and analyzed by mass spectrometry in the multiple reaction monitoring mode using the respective [M-H]- ions, m/z 410/348 for fluvastatin and m/z 480/418 for the internal standard. The assay exhibited a linear dynamic range of 2-500 ng/mL for fluvastatin in human plasma. The lower limit of quantification was 2 ng/mL with a relative standard deviation of less than 5%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 1.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.

Liquid chromatography/negative ion electrospray tandem mass spectrometry method for the quantification of rosuvastatin in human plasma: Application to a pharmacokinetic study

“…Most of the published LC-MS/MS methods [11][12][13][14] were based on positive electrospray detection, which provided a sensitivity at LLOQ of ≥0.1 ng/ml, using a plasma sample volume of 0.25-1.7 ml. The negative ionization mode was scarcely mentioned except one report in which rosuvastatin was served as internal standard (IS), where the spiked plasma concentration of rosuvastatin was 200 ng/ml [15]. Some methods [11,13] have been successfully applied to characterize the clinical pharmacokinetic profiles of rosuvastatin after 10 mg or higher doses, excepting a more recently described LC-MS/MS method [14], which was applied to determine plasma concentrations of rosuvastatin after an oral administration of 5 mg dose.…”

LC–MS/MS method for the determination of several drugs used in combined cardiovascular therapy in human plasma

“…In this work, a simple and fast method for the determination of drugs used in combined cardiovascular therapy has been developed, considering the most prescribed drugs in our geographical area: atenolol, bisoprolol (␤- 0 5 9 5 2 2 8 7 2 6 4 0 6 0 10 90 10 15 90 10 16 5 95 20 5 95 blockers), hydrochlorothiazide, chlorthalidone (diuretics), salicylic acid (active metabolite of aspirin, antiplatelet), enalapril (ACEI) and its active metabolite enalaprilat, valsartan (ARA-II), and fluvastatin (statin). Although most of these drugs have been individually analyzed in plasma by LC coupled to mass spectrometry techniques [10][11][12][13][14], in this work, a simple and fast LC-MS/MS method has been developed for their simultaneous analysis in human plasma. The suitability of the method has been demonstrated by validation, carried out following the guidelines proposed by Food and Drug Administration (FDA) [15] and International Conference on Harmonisation (ICH) [16].…”

Development and validation of a GC-FID assay for determination of fluvastatin in pharmaceutical preparations

“…[1][2][3][4] FLU is used in the treatment of hypercholestrolemia, 5,6 and treatment with statin drugs decreases the risk of cardiovascular diseases, in addition to mortality. 7 FLU has been determined by high performance liquid chromatographic methods with UV detection, 8 fluorometric detection [9][10][11][12] and mass spectrometric detection 13,14 in human plasma. A few methods such as spectrophotometric, 15 electrometric 16,17 and electrophoretic 18,19 have been reported for the assay of FLU in pharmaceutical preparations.…”