Measurement of flecainide plasma concentrations by high performance liquid chromatography with fluorescence detection.
A simple, rapid, selective, and sensitive high performance liquid chromatographic method for the assay of flecainide in plasma has been developed. The method includes extraction of plasma samples via activated BondElut C8 disposable columns with methanol at pH 9.0 after addition of internal standard, and initially on column washings of samples at pH 9.0 with water and acetonitrile. The obtained methanolic extract is directly injected into the liquid chromatograph. Separation is performed using a Radial-Pak C18 5-micron column operating in combination with a radial compression separation unit and a methanol:25% ammonia (99.9:0.1, v/v) mobile phase. The eluent is monitored with a fluorescence detector operating at an excitation wavelength of 293 nm and an emission filter of 340 nm. Endogenous substances or a variety of drugs concomitantly used in flecainide therapy do not interfere with the assay. The plasma calibration curve of flecainide is linear in the concentration range of 25 to 1000 ng/mL. The mean recovery of flecainide from plasma with concentrations varying from 50 to 1000 ng/mL is 100 +/- 3%. The limit of sensitivity of the assay is 10 ng/mL. The intra- and inter-day coefficient of variation for replicate analysis of spiked plasma samples is less than 5 and 10% respectively. The mean plasma flecainide level in 48 patients, using a mean oral daily maintenance dose of 283 +/- 72 mg for at least one week was 557 +/- 250 ng/mL. The relationship between the steady state flecainide plasma concentration and daily flecainide maintenance dose in mg in 48 patients was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
D000889:Anti-Arrhythmia Agents / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005424:Flecainide; D005453:Fluorescence; D006801:Humans; D000432:Methanol / Q000097:blood; D010880:Piperidines / Q000097:blood*; D011342:Procainamide / Q000097:blood
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D005424:Flecainide; D011342:Procainamide; D000432:Methanol