Measurement of flecainide acetate in human plasma by an extraction spectrophotofluorometric method

A fluorometric method for the quantitation of 2,5-bis-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)benzamide acetate (R-818, flecainide acetate) in human plasma has been developed. The minimum quantifiable concentration of flecainide acetate by this method is 25 ng/ml with a 2 ml plasma sample; a slightly modified procedure which also requires the use of a microcell in the spectrophotofluorometer further increases the maximum sensitivity to 12.5 ng/ml. The precision, expressed as relative standard deviation is 2.9, 0.7, 5.6, 3.5, and 4.3% for 75, 150, 250, 500, and 700 ng flecainide acetate/ml, respectively. The accuracy, expressed as relative error, is -6.7, -3.3, -0.4, +4.4, and -0.4%, respectively, for the corresponding concentrations specified above. The relative standard deviations for the inter-day variation are 19, 7, 9, 9, 8, 10, 13, 12, and 9% for the 25, 50, 100, 200, 300, 400, 600, 800, and 1000 ng/ml standards, respectively. Preliminary data indicate that propranolol and quinidine interfere with this method while procainamide, disopyramide, hydralazine, methyldopa, diazepam, hydrochlorothiazide, and sulfinpyrazone exhibit little or no interference. The results of the analyses of clinical samples by the fluorometric method agree well with an established GLC method. Thus, the quality of the fluorometric method is considered adequate for estimating plasma flecainide acetate levels during drug therapy in most non-research settings, if careful consideration is given to possible interference by other drugs.