A Quantitative LC-MS/MS Method for Determination of Liposomal Amphotericin B in Rat Plasma and Tissues and its Application to a Toxicokinetic and Tissue Distribution Study

两性霉素B 化学 色谱法 蛋白质沉淀 药代动力学 脂质体 洗脱 检出限 分析物 药理学 抗真菌 皮肤病科 生物化学 医学
作者
Quanyu Xu,Yueyue Qian,Ye Yuan,Qing Shao,Xuejun He,Hongqun Qiao
出处
期刊:Current Pharmaceutical Analysis [Bentham Science]
卷期号:16 (7): 880-891
标识
DOI:10.2174/1573412915666190415150644
摘要

Background:: Among the existing antifungal drugs, Amphotericin B is the first drug in the treatment of systemic fungal infections. However, its large adverse reactions limit the clinical application and Liposome Amphotericin B resolves the problem. Objective:: In the present study, a rapid, simple, sensitive and efficient method based on LCMS/ MS for determination of liposomal Amphotericin B in rat plasma and tissue samples using natamycin as the internal standard has been developed and validated. Methods: The analytical samples contain the plasma and various tissues disposed of by protein precipitation and determination of liposomal Amphotericin B by an LC-MS/MS. Chromatographic separation was achieved on a Poroshell 120 EC-C18 column (4.6 mm × 50 mm, 2.7 μm) with 10 mmol/L ammonium acetate in water-acetonitrile by gradient elution at a flow rate of 0.7 mL/min. The MS analysis was conducted in positive electrospray ionization with Multiple Reaction Monitoring (MRM). Results:: The calibration curves of plasma and tissues showed good linear range from 50 to 10000 ng/mL. The analytical samples containing plasma and tissues were stable under different storage conditions and temperature. Conclusions: : The developed LC-MS/MS method has been successfully applied to the studies of toxicokinetics and tissue distribution after intravenous injection of liposomal Amphotericin B to rats.
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