Identification and quantification of poly(amidoamine) PAMAM dendrimers of generations 0 to 3 by liquid chromatography/hybrid quadrupole time‐of‐flight mass spectrometry in aqueous medium

Ulaszewska, Marynka; Hernando, M.D.; Moreno, Ana Uclés; García, Antonio Burgos; García‐Calvo, Eloy; Fernández‐Alba, Amadeo R.

doi:10.1002/rcm.6498

Cited by 15 publications

(17 citation statements)

References 33 publications

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“…1 Dendrimers have a well-defined branching architecture consisting of an initiator core, a radiating interior structural layer composed of repeating generations (G0-G10), and terminal functional groups attached to the outermost generation ( Figure 1). 2,3 Subsequent generations increase in diameter, the number of terminal functional groups, and the number of vacancies available to carry therapeutics. [4][5][6][7] The low polydispersity index and the ability to precisely control their surface chemistry make dendrimers useful for medical imaging, enhancing the solubility and/or bioavailability of drugs, brain-target drug therapy, and specific targeting mechanism for anti-cancer therapeutics and gene therapy.…”

Section: Introductionmentioning

confidence: 99%

Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

Pryor¹,

Harper²,

Harper³

2014

IJN

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Dendrimers are well-defined, polymeric nanomaterials currently being investigated for biomedical applications such as medical imaging, gene therapy, and tissue targeted therapy. Initially, higher generation (size) dendrimers were of interest because of their drug carrying capacity. However, increased generation was associated with increased toxicity. The majority of studies exploring dendrimer toxicity have focused on a small range of materials using cell culture methods, with few studies investigating the toxicity across a wide range of materials in vivo. The objective of the present study was to investigate the role of surface charge and generation in dendrimer toxicity using embryonic zebrafish ( Danio rerio ) as a model vertebrate. Due to the generational and charge effects observed at the cellular level, higher generation cationic dendrimers were hypothesized to be more toxic than lower generation anionic or neutral dendrimers with the same core composition. Polyamidoamine (PAMAM) dendrimers elicited significant morbidity and mortality as generation was decreased. No significant adverse effects were observed from the suite of thiophosphoryl dendrimers studied. Exposure to ≥50 ppm cationic PAMAM dendrimers G3-amine, G4-amine, G5-amine, and G6-amine caused 100% mortality by 24 hours post-fertilization. Cationic PAMAM G6-amine at 250 ppm was found to be statistically more toxic than both neutral PAMAM G6-amidoethanol and anionic PAMAM G6-succinamic acid at the same concentration. The toxicity observed within the suite of varying dendrimers provides evidence that surface charge may be the best indicator of dendrimer toxicity. Dendrimer class and generation are other potential contributors to the toxicity of dendrimers. Further studies are required to better understand the relative role each plays in driving the toxicity of dendrimers. To the best of our knowledge, this is the first in vivo study to address such a broad range of dendrimers.

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Section: Introductionmentioning

confidence: 99%

Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

Pryor¹,

Harper²,

Harper³

2014

IJN

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“…The ions m/z 425.3 and 311.2 can be formed by the sequential loss of 114 Da. This characteristic fragmentation, obtained via neutral loss of 114 Da, was used for confirmation of PAMAM G0 by monitoring two SRM transitions, 539.3 → 425.3 (SRM 1 ), 539.3 → 311.2 (SRM 2 ), and SRM ratio (SRM 2 /SRM 1 ). The most intense SRM transition, 539.3 → 425.3 (SRM 1 ), was selected for quantitation purposes.…”

Section: Resultsmentioning

confidence: 99%

“…Both the ESI and the TOF technology have proved highly efficient in promoting the ionization of PAMAM dendrimers and in resolving the multiply charged species formed . Added selectivity, due to the high mass‐resolving power, the mass accuracy and the tandem mass spectrometry (MS/MS) operation mode of LC/ESI‐QTOF‐MS, has been an advantage in screening complex aqueous mixtures and in overcoming matrix effects in dendrimer analysis …”

mentioning

confidence: 99%

Quantitative determination of poly(amidoamine) dendrimers in urine by liquid chromatography/electrospray ionization hybrid quadrupole linear ion trap mass spectrometry

Uclés

Bueno

Ulaszewska

et al. 2013

Rapid Comm Mass Spectrometry

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The developed method has demonstrated a capability for the identification and quantification of PAMAM dendrimer nanoparticles in a complex liquid matrix. The use of an LC/ESI-QqLIT-MS system, of modest m/z range and unit resolution, offers an alternative in the analysis of lower generation PAMAM dendrimers between mass analyzers of higher resolution and the conventional LC-UV method that is commonly applied for dendrimer quantification, but which lacks sufficient identification capacity. Copyright © 2013 John Wiley & Sons, Ltd.

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“…The flow rate was 500 µl min −1 . A linear gradient was set from 10% to 100% of acetonitrile in 12 min and then maintained at 100% for 5 min . The data acquisition and processing in the LC‐ESI‐QTOF‐MS system were carried out using Analyst® TF 1.5 and PeakView TM (AB SCIEX) software.…”

Section: Methodsmentioning

confidence: 99%

“…A linear gradient was set from 10% to 100% of acetonitrile in 12 min and then maintained at 100% for 5 min. [14,17,18] The data acquisition and processing in the LC-ESI-QTOF-MS system were carried out using Analyst® TF 1.5 and PeakView TM (AB SCIEX) software. PeakView ™ incorporates tools to display, filter and process IDA data.…”

Section: Sample Preparation and Lc-esi-qtof-ms/ms Analysismentioning

confidence: 99%

Simultaneous screening of targeted and non‐targeted contaminants using an LC‐QTOF‐MS system and automated MS/MS library searching

et al. 2014

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Simultaneous high-resolution full-scan and tandem mass spectrometry (MS/MS) analysis using time of flight mass spectrometry brings an answer for increasing demand of retrospective and non-targeted data analysis. Such analysis combined with spectral library searching is a promising tool for targeted and untargeted screening of small molecules. Despite considerable extension of the panel of compounds of tandem mass spectral libraries, the heterogeneity of spectral data poses a major challenge against the effective usage of spectral libraries. Performance evaluation of available LC-MS/MS libraries will significantly increase credibility in the search results. The present work was aimed to evaluate fluctuation of MS/MS pattern, in the peak intensities distribution together with mass accuracy measurements, and in consequence, performance compliant with ion ratio and mass error criteria as principles in identification processes for targeted and untargeted contaminants at trace levels. Matrix effect and ultra-trace levels of concentration (from 50 ng l(-1) to 1000 ng l(-1) were evaluated as potential source of inaccuracy in the performance of spectral matching. Matrix-matched samples and real samples were screened for proof of applicability. By manual review of data and application of ion ratio and ppm error criteria, false negatives were obtained; this number diminished when in-house library was used, while with on-line MS/MS databases 100% of positive samples were found. In our experience, intensity of peaks across spectra was highly correlated to the concentration effect and matrix complexity. In turn, analysis of spectra acquired at trace concentrations and in different matrices results in better performance in providing correct and reliable identification.

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Identification and quantification of poly(amidoamine) PAMAM dendrimers of generations 0 to 3 by liquid chromatography/hybrid quadrupole time‐of‐flight mass spectrometry in aqueous medium

Cited by 15 publications

References 33 publications

Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

Quantitative determination of poly(amidoamine) dendrimers in urine by liquid chromatography/electrospray ionization hybrid quadrupole linear ion trap mass spectrometry

Simultaneous screening of targeted and non‐targeted contaminants using an LC‐QTOF‐MS system and automated MS/MS library searching

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