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.

中文翻译：

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通过验证的UPLC-Q-TOF-MS方法，研究了天然肠球菌感染的绵羊体内脂质体阿苯达唑的药代动力学和组织分布。

世卫组织推荐阿苯达唑（ABZ）是治疗棘球co虫病的一线药物。为了解决阿苯达唑的不良生物利用度，制定了脂质体阿苯达唑，该药物在我们医院已有多年使用。在这项研究中，开发了一种灵敏，可靠且准确的UPLC-Q-TOF-MS方法，并已用于测定阿苯达唑及其代谢产物，阿苯达唑亚砜（ABZSO），阿苯达唑砜（ABZSO2）和阿苯达唑-2-氨基砜（ABZSO2NH2） ），以甲苯咪唑（MBZ）作为内标（IS）在天然棘球chin虫（E. granulosus）感染的绵羊血浆和组织中。用蛋白质沉淀法制备血浆和组织样品。分离在ACQUITYUPLC®BEH C18色谱柱（2.1×50 mm，1。7μm）梯度流动相，该流动相由甲醇和含有0.1％甲酸的水组成，流速为0.4 mL / min。使用正电喷雾电离（ESI）源在四极杆飞行时间（Q-TOF）高分辨率质谱仪上进行色谱分析，运行时间为6.0分钟。使用[M + H] +的目标离子，ABZ在m / z 266.096，ABZSO在m / z 282.091，ABZSO2在m / z 298.086，ABZSO2NH2在m / z 240.081，IS在m / z 296.104在目标离子上进行检测。选择性离子模式。该方法在选择性，线性，精密度，准确性，回收率，基质效应，稀释效应，残留效应，稳定性，校正曲线和LLOQ方面均得到验证。所有验证参数结果均在生物分析方法验证指南中所述的可接受范围内。该方法已成功应用于单次和多次口服10 mg / kg阿苯达唑脂质体的药代动力学研究，以及多次口服10 mg / kg阿苯达唑乳剂作为参考制剂后的组织分布研究。文章中的结果将为脂质体阿苯达唑的临床应用提供有价值的信息，并且对于将来的研究中脂质体阿苯达唑的进一步开发有益。