Sensitive method for endotoxin determination in nanomedicinal product samples

Christina Giannakou; Kukka Aimonen; Louis van Bloois; Julia Catalan; Robert E. Geertsma; Eric R. Gremmer; Wim H. de Jong; Peter H. J. Keizers; Paul L. W. J. Schwillens; Rob J. Vandebriel; Margriet V. D. Z. Park

doi:10.2217/nnm-2018-0339

Sensitive method for endotoxin determination in nanomedicinal product samples

Christina Giannakou^*, Kukka Aimonen, Louis van Bloois, Julia Catalan, Robert E. Geertsma, Eric R. Gremmer, Wim H. de Jong, Peter H. J. Keizers, Paul L. W. J. Schwillens, Rob J. Vandebriel, Margriet V. D. Z. Park

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Aim: Nanomaterials and nanomedicinal products tend to interfere with various commonly used assays, including regulatory required endotoxin detection methods for medicines. We developed a method to quantify endotoxin levels that is compatible with nanomaterials and nanomedicinal products. Materials & methods: The method is based on measuring endotoxin indirectly via 3-hydroxylated fatty acids of lipid-A, using Ultra High Performance Liquid Chromatography coupled with mass spectrometry. The outcome was related to results of the commonly used Limulus Amebocyte Lysate method. Results: The ultra high performance liquid chromatography coupled with mass spectrometry method has clear advantages compared with other endotoxin determination assays; particularly the absence of nanospecific interference. Conclusion: The method is sensitive, straightforward and accurate in determining and quantifying endotoxin in nanomedicinal product samples.

Original language	English
Pages (from-to)	1231-1246
Number of pages	16
Journal	Nanomedicine
Volume	14
Issue number	10
DOIs	https://doi.org/10.2217/nnm-2018-0339
Publication status	Published - May 2019

Keywords

fatty acids
interference
LAL assay
lipopolysaccharide
nanomaterials
nanomedicine
GAS-CHROMATOGRAPHY
BACTERIAL LIPOPOLYSACCHARIDES
MASS-SPECTROMETRY
NANOPARTICLES
NANOMATERIALS
CONTAMINATION
DOXORUBICIN
TOXICITY
DELIVERY
SYSTEMS

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10.2217/nnm-2018-0339

Cite this

@article{b56787568ea34523b84406cf8069211f,

title = "Sensitive method for endotoxin determination in nanomedicinal product samples",

abstract = "Aim: Nanomaterials and nanomedicinal products tend to interfere with various commonly used assays, including regulatory required endotoxin detection methods for medicines. We developed a method to quantify endotoxin levels that is compatible with nanomaterials and nanomedicinal products. Materials & methods: The method is based on measuring endotoxin indirectly via 3-hydroxylated fatty acids of lipid-A, using Ultra High Performance Liquid Chromatography coupled with mass spectrometry. The outcome was related to results of the commonly used Limulus Amebocyte Lysate method. Results: The ultra high performance liquid chromatography coupled with mass spectrometry method has clear advantages compared with other endotoxin determination assays; particularly the absence of nanospecific interference. Conclusion: The method is sensitive, straightforward and accurate in determining and quantifying endotoxin in nanomedicinal product samples.",

keywords = "fatty acids, interference, LAL assay, lipopolysaccharide, nanomaterials, nanomedicine, GAS-CHROMATOGRAPHY, BACTERIAL LIPOPOLYSACCHARIDES, MASS-SPECTROMETRY, NANOPARTICLES, NANOMATERIALS, CONTAMINATION, DOXORUBICIN, TOXICITY, DELIVERY, SYSTEMS",

author = "Christina Giannakou and Kukka Aimonen and {van Bloois}, Louis and Julia Catalan and Geertsma, {Robert E.} and Gremmer, {Eric R.} and {de Jong}, {Wim H.} and Keizers, {Peter H. J.} and Schwillens, {Paul L. W. J.} and Vandebriel, {Rob J.} and Park, {Margriet V. D. Z.}",

note = "Funding Information: This work was supported by the project E/132058 {\textquoteleft}Nanomedicine benefits & risks{\textquoteright}, funded by the research program {\textquoteleft}Onderzoek-sprogramma Geneesmiddelenketen{\textquoteright}, a collaboration of Dutch governmental bodies involved in medicine evaluation, authorization and monitoring and the EU FP7 project GUIDEnano grant agreement number 604387. The authors have no other relevant affil- iations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: {\textcopyright} 2019 Future Medicine Ltd.",

year = "2019",

month = may,

doi = "10.2217/nnm-2018-0339",

language = "English",

volume = "14",

pages = "1231--1246",

journal = "Nanomedicine",

issn = "1743-5889",

publisher = "Future Medicine Ltd.",

number = "10",

}

TY - JOUR

T1 - Sensitive method for endotoxin determination in nanomedicinal product samples

AU - Giannakou, Christina

AU - Aimonen, Kukka

AU - van Bloois, Louis

AU - Catalan, Julia

AU - Geertsma, Robert E.

AU - Gremmer, Eric R.

AU - de Jong, Wim H.

AU - Keizers, Peter H. J.

AU - Schwillens, Paul L. W. J.

AU - Vandebriel, Rob J.

AU - Park, Margriet V. D. Z.

N1 - Funding Information: This work was supported by the project E/132058 ‘Nanomedicine benefits & risks’, funded by the research program ‘Onderzoek-sprogramma Geneesmiddelenketen’, a collaboration of Dutch governmental bodies involved in medicine evaluation, authorization and monitoring and the EU FP7 project GUIDEnano grant agreement number 604387. The authors have no other relevant affil- iations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: © 2019 Future Medicine Ltd.

PY - 2019/5

Y1 - 2019/5

N2 - Aim: Nanomaterials and nanomedicinal products tend to interfere with various commonly used assays, including regulatory required endotoxin detection methods for medicines. We developed a method to quantify endotoxin levels that is compatible with nanomaterials and nanomedicinal products. Materials & methods: The method is based on measuring endotoxin indirectly via 3-hydroxylated fatty acids of lipid-A, using Ultra High Performance Liquid Chromatography coupled with mass spectrometry. The outcome was related to results of the commonly used Limulus Amebocyte Lysate method. Results: The ultra high performance liquid chromatography coupled with mass spectrometry method has clear advantages compared with other endotoxin determination assays; particularly the absence of nanospecific interference. Conclusion: The method is sensitive, straightforward and accurate in determining and quantifying endotoxin in nanomedicinal product samples.

AB - Aim: Nanomaterials and nanomedicinal products tend to interfere with various commonly used assays, including regulatory required endotoxin detection methods for medicines. We developed a method to quantify endotoxin levels that is compatible with nanomaterials and nanomedicinal products. Materials & methods: The method is based on measuring endotoxin indirectly via 3-hydroxylated fatty acids of lipid-A, using Ultra High Performance Liquid Chromatography coupled with mass spectrometry. The outcome was related to results of the commonly used Limulus Amebocyte Lysate method. Results: The ultra high performance liquid chromatography coupled with mass spectrometry method has clear advantages compared with other endotoxin determination assays; particularly the absence of nanospecific interference. Conclusion: The method is sensitive, straightforward and accurate in determining and quantifying endotoxin in nanomedicinal product samples.

KW - fatty acids

KW - interference

KW - LAL assay

KW - lipopolysaccharide

KW - nanomaterials

KW - nanomedicine

KW - GAS-CHROMATOGRAPHY

KW - BACTERIAL LIPOPOLYSACCHARIDES

KW - MASS-SPECTROMETRY

KW - NANOPARTICLES

KW - NANOMATERIALS

KW - CONTAMINATION

KW - DOXORUBICIN

KW - TOXICITY

KW - DELIVERY

KW - SYSTEMS

U2 - 10.2217/nnm-2018-0339

DO - 10.2217/nnm-2018-0339

M3 - Article

C2 - 31124759

SN - 1743-5889

VL - 14

SP - 1231

EP - 1246

JO - Nanomedicine

JF - Nanomedicine

IS - 10

ER -