Rapid Quantitation Of Flecainide In Human Plasma For Therapeutic Drug Monitoring Using Liquid Chromatography And Time-Of-Flight Mass Spectrometry

Background: Measurement of flecainide is useful to optimize dosage and minimize risks of toxicity. Furthermore, there is a need for urgent sample analysis when flecainide is used in transplacental therapy for fetal tachycardia. To this end, we have developed and validated a rapid assay for the measurement of flecainide in human plasma or serum, using a small sample volume (50 mu L).Methods: After a simple deproteination with zinc sulfate and methanol, prepared samples were injected onto a short (30 mm) analytical column and eluted using a rapid gradient elution. Detection was performed using time-of-flight mass spectrometry. Flecainide was quantified using flecainide-D-4 as internal standard, with both compounds extracted from the total ion chromatogram using a +/- 5 ppm extraction window based on the theoretical m/z values for the protonated ions.Results: The assay was linear over a putative therapeutic range (100-1500 mcg/L). Between- and within-assay imprecision and accuracy were <4.6% and 94.8%-110.0%, respectively. Matrix effects were minimal and were compensated for by flecainide-D-4. There were no effects due to hemolysis or lipemia, and no carryover was apparent. Total analysis time was just 1.2 minutes (72 seconds).Conclusions: We have developed and validated a rapid method for the analysis of flecainide. The method is particularly suited for flecainide therapeutic drug monitoring, when analyzing samples from mothers receiving flecainide for the treatment of fetal tachycardia.