title: A systematic review and critical comparison of internal standards for the routine liquid chromatographic assay of amiodarone and desethylamiodarone.
abstract: Despite potential adverse effects, clinical use of amiodarone is increasing because of its efficacy in treating arrhythmias. Thus there is a continued need for a rapid, practical amiodarone assay to better study the relationship between serum concentrations and clinical effects and to guide safer dosing. Because the most widely used internal standard, L8040, is no longer available, a systematic comparison of potential alternatives was undertaken based on physicochemical and chromatographic characteristics. All amiodarone assays indexed on Medline were reviewed to produce a list of alternatives and five other potential substances considered based on previous experiences. An isocratic high-performance liquid chromatographic method was modified to allow simultaneous resolution of multiple compounds. The internal standard was expected to perform well in the solid-phase extraction of small sample volumes. No commercially available substances were able to duplicate all the advantages of L8040. Tamoxifen, the most acceptable alternative, was used to develop an assay to measure amiodarone and desethylamiodarone at concentrations as low as 0.25 mg/L in 100 microliters of serum (5 ng detected in a 20 microliters injection). Standard curves were linear over the range of concentrations found in our patients (0.25 to 8 mg/L), within-run coefficients of variation (CVs) averaged 5.3% for amiodarone and 2.9% for desethylamiodarone, and between-run CVs were 4.5% for amiodarone and 1.6% for desethylamiodarone.
authors.affiliation: Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: P T
authors.initials: PT
authors.lastname: Pollak
mesh_terms: D000638:Amiodarone / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry; D000889:Anti-Arrhythmia Agents / Q000032:analysis* / Q000737:chemistry; D015764:Bepridil / Q000032:analysis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards*; D018492:Dopamine Antagonists / Q000032:analysis / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000592:standards*; D004965:Estrogen Antagonists / Q000032:analysis / Q000737:chemistry; D013629:Tamoxifen / Q000032:analysis / Q000737:chemistry; D014268:Trifluoperazine / Q000032:analysis / Q000737:chemistry
chemical_list: D000889:Anti-Arrhythmia Agents; D018492:Dopamine Antagonists; D004965:Estrogen Antagonists; D013629:Tamoxifen; D014268:Trifluoperazine; D015764:Bepridil; C036116:desethylamiodarone; D000638:Amiodarone