Title: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
VOLUME: 16 ISSUE: 7
Author(s):Quanyu Xu, Yueyue Qian, Yanjuan Yuan, Qing Shao, Xuejun He and Hongqun Qiao*
Affiliation:School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, Jiangsu Provincial Institute Of Materia Medica, Nanjing 211816, Jiangsu Provincial Institute Of Materia Medica, Nanjing 211816, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816
Keywords:Liposomal, Amphotericin B, LC-MS/MS, toxicokinetic, tissudistribution, rats, intravenous injection.
Abstract:
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.
Conclusion: 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.