Sensitive assay for the determination of fluvastatin in plasma utilizing high-performance liquid chromatography with fluorescence detection

The authors describe a rapid, useful, specific, and very sensitive high-performance liquid chromatographic assay for the determination of fluvastatin (FV) level using atorvastatin as the internal standard (IS). After a simple deproteinization of 1.0 mL of plasma with acetonitrile, the drug and IS were extracted with tert-methyl butyl ether (TMBE). An efficient separation was performed using an 8 mm x 10 cm Nova Pak C-18 4-mum particle size radial compression cartridge. The mobile phase consisted of an aqueous solution containing 20 mmol/L dibasic sodium dihydrogen phosphate with I mmol/L sodium lauryl sulfate adjusted to pH 7 with phosphoric acid and acetonitrile (70:30 v/v) delivered at a flow rate of 1.0 mL/min. The compounds of interest were detected using a fluorescence detector with the excitation wavelength set at 305 nm and the emission at 380 nm. Under these conditions, the retention times for FV and IS were 8.8 and 10.6 minutes, respectively. The concentration of FV in plasma was linear (r > 0.999) for the wide range that was examined (0.5-1,000 ng/mL). The recovery ranged from 88% to 96%. This sensitive, rapid, and simple analytical method gives accurate results over the wide range of concentrations examined. This method is used currently for clinical therapeutic monitoring and pharmacokinetic studies of FV in patients with hypercholesterolemia.