title: Liquid chromatographic assay with fluorescence detection to determine ajmaline in serum from patients with suspected Brugada syndrome.
abstract: Ajmaline is a sodium channel blocking, class 1A anti-arrhythmic drug. It has gained renewed interest in the field of cardiology as a diagnostic agent to reveal the electrocardiographic characteristics in patients with suspected Brugada syndrome. We developed a simple and precise high-performance liquid chromatographic assay to determine ajmaline in serum of patients. The samples were pre-treated using protein precipitation with perchloric acid and the extract was injected into the chromatographic system. The system consisted of an end-capped octadecyl silica column with isocratic elution using perchloric acid in a water-acetonitrile mixture. Ajmaline was detected by fluorescence at 290 and 355 nm for excitation and emission, respectively. The assay was validated in a 21-5300 ng/ml concentration range, the lower limit of quantification was 25 ng/ml. Within day precisions were 1.3-3.9%, between day precisions 2-7% and accuracies were between 95 and 99% for the whole calibration range. The drug was shown to be chemically stable under all relevant conditions. This assay has been successfully applied to pharmacokinetic-pharmacodynamic evaluations of intravenous ajmaline administration to patients with suspected Brugada syndrome.
authors.affiliation: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands. R.W.Sparidans@uu.nl
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Sparidans
authors.forename: Pim
authors.initials: P
authors.lastname: Langendijk
authors.forename: Eric
authors.initials: E
authors.lastname: Boers
authors.forename: Erik
authors.initials: E
authors.lastname: van Kan
authors.forename: Hanno L
authors.initials: HL
authors.lastname: Tan
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000368:Aged; D000404:Ajmaline / Q000097:blood* / Q000493:pharmacokinetics; D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000493:pharmacokinetics; D053840:Brugada Syndrome / Q000097:blood*; D002138:Calibration; D002853:Chromatography, Liquid / Q000295:instrumentation* / Q000379:methods*; D004355:Drug Stability; D005453:Fluorescence; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D000889:Anti-Arrhythmia Agents; D000404:Ajmaline