Kunicki Paweł K, Stocki Adam
Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
Int J Mol Sci. 2025 May 1;26(9):4304. doi: 10.3390/ijms26094304.
Dronedarone (DRO) is an antiarrhythmic drug that should be used under close supervision, and therapeutic drug monitoring (TDM) may be one of the tools supporting pharmacotherapy. The aim of our study was to develop an economical HPLC method for determining DRO and its active metabolite debutyldronedarone (DBD) in human plasma. An HPLC isocratic system with a manual injector was applied. The separation was performed on a Supelcosil LC-CN column (150 × 4.6 mm, 5 µm) at an ambient temperature. The mobile phase was a mixture of CHOH:CHCN:HO:0.5 M KHPO (170:85:237.2:7.8 (/)) + 0.1 mL 85% HPO pumped at a flow rate of 1.8 mL/min. The UV detection was set at λ = 290 nm. A methyl tert-butyl ether was used for the extraction from a 0.4 mL alkalized plasma sample. The analytes were eluted at retention times of 4.0 min, 5.2 min and 6.0 min for DBD, internal standard bepridil and DRO, respectively. The method was calibrated in the range of 10-1000 ng/mL for both DRO and DBD. The adequate specificity, accuracy and precision were demonstrated in accordance with EMA guidelines, i.e., ≤15% (≤20% for the LLOQ), which ensures the reliability of the measurements. This method can be recommended for laboratories with basic HPLC equipment for TDM, adherence assessments and even in PK studies during chronic DRO therapy.
决奈达隆（DRO）是一种抗心律失常药物，应在密切监测下使用，治疗药物监测（TDM）可能是支持药物治疗的工具之一。我们研究的目的是开发一种经济的高效液相色谱法（HPLC），用于测定人血浆中的DRO及其活性代谢物去丁基决奈达隆（DBD）。采用了带有手动进样器的HPLC等度系统。在室温下，于Supelcosil LC-CN柱（150×4.6 mm，5 µm）上进行分离。流动相为CHOH:CHCN:HO:0.5 M KHPO（170:85:237.2:7.8（/））+ 0.1 mL 85% HPO，以1.8 mL/min的流速泵送。紫外检测设定在λ = 290 nm。使用甲基叔丁基醚从0.4 mL碱化血浆样品中进行萃取。对于DBD、内标苄普地尔和DRO，分析物的保留时间分别为4.0分钟、5.2分钟和6.0分钟。该方法针对DRO和DBD在10 - 1000 ng/mL范围内进行了校准。根据欧洲药品管理局（EMA）指南证明了其具有足够的特异性、准确性和精密度，即≤15%（LLOQ时≤20%），这确保了测量的可靠性。该方法可推荐给配备基本HPLC设备的实验室用于TDM、依从性评估，甚至在决奈达隆长期治疗期间的药代动力学（PK）研究。
