A high-throughput LC-MS/MS method for simultaneous analysis of albendazole, albendazole sulfoxide and albendazole sulfone in human plasma

Abstract

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.