The development and assessment of high-throughput mass spectrometry-based methods for the quantification of a nanoparticle drug delivery agent in cellular lysate

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DOIResolve DOI: http://doi.org/10.1002/jms.3444
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TypeArticle
Journal titleJournal of Mass Spectrometry
ISSN1076-5174
Volume49
Issue11
Pages11711180; # of pages: 10
SubjectChromatography; Desorption; Gene transfer; Ionization; Ionization of liquids; Liquids; Matrix algebra; Spectrometry; Surface active agents; Throughput; Tissue culture; Desorption electrospray ionization; Fast chromatography; Gemini surfactant; Matrix assisted laser desorption ionization; Electrospray ionization; lipid; n,n bis(dimethylhexadecyl) 1,3 propane diammonium; nanoparticle; surfactant; cell extract; analytic method; cell interaction; cell lysate; collisionally activated dissociation; controlled study; intermethod comparison; mass spectrometry; matrix assisted laser desorption ionization time of flight mass spectrometry; qualitative analysis; quantitative analysis; tandem mass spectrometry; tissue culture; cell line; drug delivery system; genetic transfection; high throughput screening; liquid chromatography; metabolism; reproducibility; sensitivity and specificity; statistical model; Linear Models; Pharmaceutical Preparations
AbstractThe safe use of lipid-based drug delivery agents requires fast and sensitive qualitative and quantitative assessment of their cellular interactions. Many mass spectrometry (MS) based analytical platforms can achieve such task with varying capabilities. Therefore, four novel high-throughput MS-based quantitative methods were evaluated for the analysis of a small organic gene delivery agent: N,N-bis(dimethylhexadecyl)-1,3-propane-diammonium dibromide (G16-3). Analysis utilized MS instruments that detect analytes using low-resolution tandem MS (MS/MS) analysis (i.e. QTRAP or linear ion trap in this work) or high-resolution MS analysis (i.e. time of flight (ToF) or Orbitrap). Our results indicate that the validated fast chromatography (FC)-QTRAP-MS/MS, FC- LTQ-Orbitrap-MS, desorption electrospray ionization-collision-induced dissociation (CID)-MS/MS and matrix assisted laser desorption ionization-ToF/ToF-MS MS methods were superior in the area of method development and sample analysis time to a previously developed liquid chromatography (LC)-CID-MS/MS. To our knowledge, this is the first evaluation of the abilities of five MS-based quantitative methods that target a single pharmaceutical analyte. Our findings indicate that, in comparison to conventional LC-CID-MS/MS, the new MS-based methods resulted in a (1) substantial reduction in the analysis time, (2) reduction in the time required for method development and (3) production of either superior or comparable quantitative data. The four new high-throughput MS methods, therefore, were faster, more efficient and less expensive than a conventional LC-CID-MS/MS for the quantification of the G16-3 analyte within tissue culture. When applied to cellular lysate, no significant change in the concentration of G16-3 gemini surfactant within PAM212 cells was observed between 5 and 53 h, suggesting the absence of any metabolism/excretion from PAM212 cells.
Publication date
PublisherWiley
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC)
Peer reviewedYes
NPARC number21275446
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Record identifier85a9f48d-0663-40e2-98ca-d607d080148a
Record created2015-07-14
Record modified2016-05-09
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