Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

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
Buy
SDC

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: lewis.couchman@bioanalytics.co.uk).

The authors declare no conflict of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.drug-monitoring.com).

Received October 01, 2018

Accepted October 30, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.