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Rapid Quantitation of Flecainide in Human Plasma for Therapeutic Drug Monitoring Using Liquid Chromatography and Time-of-Flight Mass Spectrometry

Rahman, Mohammed*,†; Couchman, Lewis, PhD*,‡; Povstyan, Valentyna, BSc*; Bainbridge, Verity, BSc*; Kipper, Karin, PhD*,§; El-Nahhas, Toqa, PhD*,¶; Johnston, Atholl, PhD*,¶; Holt, David, DSc (Med)*

doi: 10.1097/FTD.0000000000000586
Short Communication

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 µL).

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-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 (100–1500 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-D4. 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.

*Analytical Services International (ASI), St George's-University of London, Cranmer Terrace, London, United Kingdom;

Department of Chemistry, University of Surrey, Guildford, United Kingdom;

Pharmaceutical Sciences Clinical Academic Group, King's College London, London, United Kingdom;

§Institute of Chemistry, University of Tartu, Tartu, Estonia; and

Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

Correspondence: Lewis Couchman, PhD, Analytical Services International, St. George's-University of London, Cranmer Terrace, London SW17 0RE, United kingdom (e-mail:

The authors declare no conflict of interest.

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Received October 01, 2018

Accepted October 30, 2018

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