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Quantitative determination and pharmacokinetic study of fusaricidin A in mice plasma and tissues using ultra-high performance liquid chromatography-tandem mass spectrometry.

J Pharm Biomed Anal. 2019 Mar 19;170:187-192

Authors: Haron MH, Avula B, Shi Q, Li XC, Ashfaq MK, Bae JY, Guan S, Hinchee M, Khan IA, Khan SI

Abstract
Fusaricidins are a family of cyclic lipodepsipeptides that convey antifungal and antibacterial activity. Fusaricidin A (FA) is one of the Fusaricidins major compounds and it is showing promising activity against fungi and bacteria. In the present study, a fast and sensitive ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for the analysis of FA in mice plasma, liver, kidney and brain tissues. The instrument was operated in positive electrospray ionization mode. Multiple reaction monitoring (MRM) mode was performed with ion pairs of m/z: 883.5→256.3, 883.5→197.2 and 883.5→72.1 for FA. The method was validated for linearity, repeatability, accuracy, stability, limits of detection (LOD) and limits of quantification (LOQ). The LOD and LOQ were 0.01 and 0.05 ng/mL for plasma and tissues, respectively. The calibration curve (10-200 ng/mL) was linear ( r2 = 0.99). Precision and accuracy values were found to be < 10% (within acceptable limit). The pharmacokinetic and tissue distribution characteristics of FA were determined in plasma, liver, kidney and brain of CD1 mice after I.V. administration of a single dose of 15 mg/kg body weight. Highest plasma concentration (Cmax) was calculated to be 4169.97 ± 50 ng/mL with a tmax of 0.08 h. The plasma clearance rate of FA was 397.6 ± 203 mL/h with a t1/2 of 2.2 ± 0.5 h and apparent volume of distribution during the terminal phase (Vz) of 979.2 ± 318 mL. The highest tissue concentration (Cmax) was found in the liver (219 ± 14 ng/mg) at a tmax of 0.08 h followed by the kidneys (38.6 ± 16 ng/mg) at tmax of 0.2 h. FA was poorly distributed to the brain with a Cmax of 0.45 ± 0.2 ng/mg and a tmax of 0.08 h. The method for quantitative analysis and pharmacokinetic data provided will support the development of various formulation approaches and therapeutic application for future clinical studies.

PMID: 30927664 [PubMed – as supplied by publisher]

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