Žideková Nela, Kertys Martin, Mokrý Juraj, Antolová Daniela, Šimeková Katarína, Rosoľanka Róbert
Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Martin, Slovak Republic.
Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Martin, Slovak Republic; Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Martin, Slovak Republic.
J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Oct 1;1264:124741. doi: 10.1016/j.jchromb.2025.124741. Epub 2025 Jul 20.
Albendazole is a benzimidazole derivative with a broad spectrum of antihelmintic activity. Its primary metabolite, albendazole sulfoxide, is responsible for the treatment's efficacy. On the other hand, it contributes to side effects and toxicity. Therefore, their quantification in plasma may increase therapeutic success and reduce associated risks by maintaining values within the therapeutic range. The present study introduces an LC-MS/MS method for the simultaneous quantification of albendazole, albendazole sulfoxide, and albendazole sulfone in human plasma. A simple and sensitive LC-MS/MS method was developed to monitor the plasma levels of albendazole (0.25-200 ng/mL), albendazole sulfoxide (5-3500 ng/mL), and albendazole sulfone (0.5-500 ng/mL) with a coefficient of variation below 7 %. A one-step extraction procedure using an Ostro™ plate was applied, and the extracts were analysed by gradient elution followed by detection on a mass spectrometer in multiple reaction monitoring mode. The method offers several significant advantages, including a low sample volume (50 μL), a short run time (4 min), and is sufficiently linear to quantify both low and high concentrations of all analytes. The method was successfully validated according to the ICH guideline M10 on bioanalytical method validation, covering selectivity, linearity of the calibration curve, lower limit of quantification (LLOQ), accuracy, precision, dilution integrity, carry-over effect, matrix effects, extraction recovery, and stability. The fully developed and validated method was used to determine albendazole, albendazole sulfoxide, and albendazole sulfone in the plasma samples of ten patients, illustrating the monitoring of albendazole treatment in patients with alveolar echinococcosis.
阿苯达唑是一种具有广谱抗蠕虫活性的苯并咪唑衍生物。其主要代谢产物阿苯达唑亚砜是治疗有效的原因。另一方面，它也会导致副作用和毒性。因此，通过将血浆中的含量维持在治疗范围内，对其进行定量分析可能会提高治疗成功率并降低相关风险。本研究介绍了一种用于同时定量人血浆中阿苯达唑、阿苯达唑亚砜和阿苯达唑砜的液相色谱-串联质谱法。开发了一种简单且灵敏的液相色谱-串联质谱法来监测阿苯达唑（0.25 - 200 ng/mL）、阿苯达唑亚砜（5 - 3500 ng/mL）和阿苯达唑砜（0.5 - 500 ng/mL）的血浆水平，变异系数低于7%。采用使用Ostro™板的一步萃取程序，萃取物通过梯度洗脱进行分析，随后在多反应监测模式下在质谱仪上进行检测。该方法具有几个显著优点，包括进样量低（50 μL）、运行时间短（4分钟），并且具有足够的线性以定量所有分析物的低浓度和高浓度。该方法已根据国际人用药品注册技术协调会（ICH）关于生物分析方法验证的M10指南成功验证，涵盖选择性、校准曲线的线性、定量下限（LLOQ）、准确度、精密度、稀释完整性、残留效应、基质效应、萃取回收率和稳定性。该完全开发并验证的方法用于测定10名患者血浆样本中的阿苯达唑、阿苯达唑亚砜和阿苯达唑砜，说明了对肺泡型棘球蚴病患者阿苯达唑治疗的监测。
