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

Author(s): Quanyu Xu, Yueyue Qian, Yanjuan Yuan, Qing Shao, Xuejun He, Hongqun Qiao*

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 7 , 2020

DOI : 10.2174/1573412915666190415150644

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Graphical Abstract:


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.

Keywords: Liposomal, Amphotericin B, LC-MS/MS, toxicokinetic, tissudistribution, rats, intravenous injection.

[1]
Nic Lochlainn, L.; Caffrey, P. Phosphomannose isomerase and phosphomannomutase gene disruptions in Streptomyces nodosus: impact on amphotericin biosynthesis and implications for glycosylation engineering. Metab. Eng., 2009, 11(1), 40-47.
[http://dx.doi.org/10.1016/j.ymben.2008.08.007] [PMID: 18824121]
[2]
Revie, N.M.; Iyer, K.R.; Robbins, N.; Cowen, L.E. Antifungal drug resistance: evolution, mechanisms and impact. Curr. Opin. Microbiol., 2018, 45, 70-76.
[http://dx.doi.org/10.1016/j.mib.2018.02.005] [PMID: 29547801]
[3]
Marcos-Zambrano, L.J.; Escribano, P.; Bouza, E.; Guinea, J. Comparison of the antifungal activity of micafungin and amphotericin B against Candida tropicalis biofilms. J. Antimicrob. Chemother., 2016, 71(9), 2498-2501.
[http://dx.doi.org/10.1093/jac/dkw162] [PMID: 27147303]
[4]
Bern, C.; Adler-Moore, J.; Berenguer, J.; Boelaert, M.; den Boer, M.; Davidson, R.N.; Figueras, C.; Gradoni, L.; Kafetzis, D.A.; Ritmeijer, K.; Rosenthal, E.; Royce, C.; Russo, R.; Sundar, S.; Alvar, J. Liposomal amphotericin B for the treatment of visceral leishmaniasis. Clin. Infect. Dis., 2006, 43(7), 917-924.
[http://dx.doi.org/10.1086/507530] [PMID: 16941377]
[5]
Drogari-Apiranthitou, M.; Mantopoulou, F.D.; Skiada, A.; Kanioura, L.; Grammatikou, M.; Vrioni, G.; Mitroussia-Ziouva, A.; Tsakris, A.; Petrikkos, G. In vitro antifungal susceptibility of filamentous fungi causing rare infections: synergy testing of amphotericin B, posaconazole and anidulafungin in pairs. J. Antimicrob. Chemother., 2012, 67(8), 1937-1940.
[http://dx.doi.org/10.1093/jac/dks137] [PMID: 22535624]
[6]
Sosa, L.; Clares, B.; Alvarado, H.L.; Bozal, N.; Domenech, O.; Calpena, A.C. Amphotericin B releasing topical nanoemulsion for the treatment of candidiasis and aspergillosis. Nanomedicine (Lond.), 2017, 13(7), 2303-2312.
[http://dx.doi.org/10.1016/j.nano.2017.06.021] [PMID: 28712917]
[7]
Chong, G.L.M.; Broekman, F.; Polinder, S.; Doorduijn, J.K.; Lugtenburg, P.J.; Verbon, A.; Cornelissen, J.J.; Rijnders, B.J.A. Aerosolised liposomal amphotericin B to prevent aspergillosis in acute myeloid leukaemia: Efficacy and cost effectiveness in real-life. Int. J. Antimicrob. Agents, 2015, 46(1), 82-87.
[http://dx.doi.org/10.1016/j.ijantimicag.2015.02.023] [PMID: 25956843]
[8]
Sidhu, R.; Lash, D.B.; Heidari, A.; Natarajan, P.; Johnson, R.H. Evaluation of amphotericin b lipid formulations for treatment of severe Coccidioidomycosis. Antimicrob Agents Ch., 2018, 62(7), , e02293-17.
[9]
Lionakis, M.S.; Holland, S.M. Human invasive mycoses: immunogenetics on the rise. J. Infect. Dis., 2015, 211(8), 1205-1207.
[PMID: 25057047]
[10]
Cornely, O.A.; Leguay, T.; Maertens, J.; Vehreschild, M.J.G.T.; Anagnostopoulos, A.; Castagnola, C.; Verga, L.; Rieger, C.; Kondakci, M.; Härter, G.; Duarte, R.F.; Allione, B.; Cordonnier, C.; Heussel, C.P.; Morrissey, C.O.; Agrawal, S.G.; Donnelly, J.P.; Bresnik, M.; Hawkins, M.J.; Garner, W.; Gökbuget, N.; Grp, A.S. AmBiGuard Study Group. Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia. J. Antimicrob. Chemother., 2017, 72(8), 2359-2367.
[http://dx.doi.org/10.1093/jac/dkx133] [PMID: 28575414]
[11]
Wasko, P.; Luchowski, R.; Tutaj, K.; Grudzinski, W.; Adamkiewicz, P.; Gruszecki, W.I. Toward understanding of toxic side effects of a polyene antibiotic amphotericin B: fluorescence spectroscopy reveals widespread formation of the specific supramolecular structures of the drug. Mol. Pharm., 2012, 9(5), 1511-1520.
[http://dx.doi.org/10.1021/mp300143n] [PMID: 22506900]
[12]
Lee, J.W.; Amantea, M.A.; Francis, P.A.; Navarro, E.E.; Bacher, J.; Pizzo, P.A.; Walsh, T.J. Pharmacokinetics and safety of a unilamellar liposomal formulation of amphotericin B (AmBisome) in rabbits. Antimicrob. Agents Chemother., 1994, 38(4), 713-718.
[http://dx.doi.org/10.1128/AAC.38.4.713] [PMID: 8031034]
[13]
Adler-Moore, J.P.; Gangneux, J.P.; Pappas, P.G. Comparison between liposomal formulations of amphotericin B. Med. Mycol., 2016, 54(3), 223-231.
[http://dx.doi.org/10.1093/mmy/myv111] [PMID: 26768369]
[14]
Rocio, C.; Amato, V.S.; Camargo, R.A.; Tuon, F.F.; Nicodemo, A.C. Liposomal formulation of amphotericin B for the treatment of mucosal leishmaniasis in HIV-negative patients. Trans. R. Soc. Trop. Med. Hyg., 2014, 108(3), 176-178.
[http://dx.doi.org/10.1093/trstmh/tru011] [PMID: 24535153]
[15]
Zhang, Z.; Dai, X. Preparation of alginate oligosaccharide nanoliposomes and an analysis of their inhibitory effects on Caco-2 cells. IET Nanobiotechnol., 2018, 12(7), 946-950.
[http://dx.doi.org/10.1049/iet-nbt.2017.0260] [PMID: 30247135]
[16]
Liu, W.; Liu, W.L.; Liu, C.M.; Liu, J.H.; Yang, S.B.; Zheng, H.J.; Lei, H.W.; Ruan, R.; Li, T.; Tu, Z.C.; Song, X.Y. Medium-chain fatty acid nanoliposomes for easy energy supply. Nutrition, 2011, 27(6), 700-706.
[http://dx.doi.org/10.1016/j.nut.2010.06.010] [PMID: 20869208]
[17]
Chen, J.; Yan, G.J.; Hu, R.R.; Gu, Q.W.; Chen, M.L.; Gu, W.; Chen, Z.P.; Cai, B.C. Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine. Int. J. Nanomedicine, 2012, 7, 3567-3577.
[http://dx.doi.org/10.2147/IJN.S32860] [PMID: 22904620]
[18]
Harvey, R.D.; Ara, N.; Heenan, R.K.; Barlow, D.J.; Quinn, P.J.; Lawrence, M.J. Stabilization of distearoylphosphatidylcholine lamellar phases in propylene glycol using cholesterol. Mol. Pharm., 2013, 10(12), 4408-4417.
[http://dx.doi.org/10.1021/mp400140u] [PMID: 24171434]
[19]
Qin, W.; Tao, H.; Chen, Y.; Chen, Z.; Wu, N. Sensitive, accurate and simple liquid chromatography-tandem mass spectrometric method for the quantitation of amphotericin B in human or minipig plasma. J. Chromatogr. Sci., 2012, 50(7), 636-643.
[http://dx.doi.org/10.1093/chromsci/bms049] [PMID: 22562820]
[20]
food and drug administration. guidance for industry: bioanalytical method validation. us; , 2013.
[21]
van Etten, E.W.; Otte-Lambillion, M.; van Vianen, W.; ten Kate, M.T.; Bakker-Woudenberg, A.J. Biodistribution of liposomal amphotericin B (AmBisome) and amphotericin B-desoxycholate (Fungizone) in uninfected immunocompetent mice and leucopenic mice infected with Candida albicans. J. Antimicrob. Chemother., 1995, 35(4), 509-519.
[http://dx.doi.org/10.1093/jac/35.4.509] [PMID: 7628985]
[22]
Hiemenz, J.W.; Walsh, T.J. Lipid formulations of amphotericin B: recent progress and future directions. Clin. Infect. Dis., 1996, 22(Suppl. 2), S133-S144.
[http://dx.doi.org/10.1093/clinids/22.Supplement_2.S133] [PMID: 8722841]
[23]
Walsh, T.J.; Goodman, J.L.; Pappas, P.; Bekersky, I.; Buell, D.N.; Roden, M.; Barrett, J.; Anaissie, E.J. Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus species and other filamentous fungi: maximum tolerated dose study. Antimicrob. Agents Chemother., 2001, 45(12), 3487-3496.
[http://dx.doi.org/10.1128/AAC.45.12.3487-3496.2001] [PMID: 11709329]
[24]
Gubbins, P.O.; Amsden, J.R.; McConnell, S.A.; Anaissie, E.J. Pharmacokinetics and buccal mucosal concentrations of a 15 milligram per kilogram of body weight total dose of liposomal amphotericin B administered as a single dose (15 mg/kg), weekly dose (7.5 mg/kg), or daily dose (1 mg/kg) in peripheral stem cell transplant patients. Antimicrob. Agents Chemother., 2009, 53(9), 3664-3674.
[http://dx.doi.org/10.1128/AAC.01448-08] [PMID: 19546359]
[25]
Walsh, T.J.; Yeldandi, V.; McEvoy, M.; Gonzalez, C.; Chanock, S.; Freifeld, A.; Seibel, N.I.; Whitcomb, P.O.; Jarosinski, P.; Boswell, G.; Bekersky, I.; Alak, A.; Buell, D.; Barret, J.; Wilson, W. Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients. Antimicrob. Agents Chemother., 1998, 42(9), 2391-2398.
[http://dx.doi.org/10.1128/AAC.42.9.2391] [PMID: 9736569]
[26]
Nieto, J.; Alvar, J.; Rodríguez, C.; San Andrés, M.I.; San Andrés, M.D.; González, F. Comparison of conventional and lipid emulsion formulations of amphotericin B: Pharmacokinetics and toxicokinetics in dogs. Res. Vet. Sci., 2018, 117, 125-132.
[http://dx.doi.org/10.1016/j.rvsc.2017.12.005] [PMID: 29272720]


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Article Details

VOLUME: 16
ISSUE: 7
Year: 2020
Published on: 17 August, 2020
Page: [880 - 891]
Pages: 12
DOI: 10.2174/1573412915666190415150644
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