Short communication: 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. Further, 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 µL).

METHOD: Following 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 carried out using time-of-flight mass-spectrometry. Flecainide was quantified using flecainide-D4 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 (100-1,500 µg/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-D4. There were no effects due to hemolysis or lipemia, and no carryover was apparent. Total analysis time was just 1.2 minutes (72 s).

CONCLUSIONS: We have developed and validated a rapid method for the analysis of flecainide. The method is particularly suited for flecainide TDM, when analyzing samples from mothers receiving flecainide for the treatment of fetal tachycardia.