Pharmacokinetics and tissue distribution study of liposomal albendazole in naturally Echinococcus granulosus infected sheep by a validated UPLC-Q-TOF-MS method

Abstract

Albendazole (ABZ) is the first-line drug in treating echinococcosis, which is recommended by WHO. To address the poor bioavailability of albendazole, liposomal albendazole was formulated and is available in our hospital for many years. In this study, a sensitive, reliable and accurate UPLC-Q-TOF-MS method was developed and validated for the determination of albendazole and its metabolites, albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO₂) and albendazole-2-aminosulfone (ABZSO₂NH₂) in naturally echinococcus granulosus (E. granulosus) infected sheep plasma and tissues with mebendazole (MBZ) as the internal standard (IS). Plasma and tissues samples were prepared by protein precipitation method. The separation was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 μm) with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at 0.4 mL/min. The detection was performed on a quadrupole time-of-flight (Q-TOF) high-resolution mass spectrometer using positive electrospray ionization (ESI) source with a chromatographic run time of 6.0 min. The detection was operated using target ions of [M + H]⁺ at m/z 266.096 for ABZ, m/z 282.091 for ABZSO, m/z 298.086 for ABZSO₂, m/z 240.081 for ABZSO₂NH₂ and m/z 296.104 for IS in selective ion mode, respectively. This method was validated in terms of selectivity, linearity, precision, accuracy, recovery, matrix effect, dilution effect, carryover effects, stability, calibration curve and LLOQ. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. This method has been successfully applied to the pharmacokinetic study following single and multiple oral dose of 10 mg/kg liposomal albendazole, and tissue distribution study following multiple oral dose of 10 mg/kg, with emulsion albendazole as the reference preparation. The results in the article will provide valuable information for use in clinical applications of liposomal albendazole and also be beneficial for further development of liposomal albendazole in future studies.

Keywords: Echinococcus granulosus; Liposomal albendazole; Pharmacokinetics; Tissue distribution; UPLC-Q-TOF-MS.