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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

Authors

  • Maria Malgorzata Ulaszewska,

    1. IMDEA – Agua (Instituto Madrileño De Estudios Avanzados – Agua), Parque Científico Tecnológico, University of Alcalá, Alcalá de Henares, Madrid, Spain
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  • Maria Dolores Hernando,

    1. Spanish National Institute for Agricultural and Food Research and Technology, INIA, Madrid, Spain
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  • Ana Uclés Moreno,

    1. Pesticide Residue Research Group, Department of Hydrogeology and Analytical Chemistry, University of Almería, Almería, Spain
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  • Antonio Valverde García,

    1. Department of Inorganic Chemistry, University of Almería, Almería, Spain
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  • Eloy García Calvo,

    1. IMDEA – Agua (Instituto Madrileño De Estudios Avanzados – Agua), Parque Científico Tecnológico, University of Alcalá, Alcalá de Henares, Madrid, Spain
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  • Amadeo R. Fernández-Alba

    Corresponding author
    1. IMDEA – Agua (Instituto Madrileño De Estudios Avanzados – Agua), Parque Científico Tecnológico, University of Alcalá, Alcalá de Henares, Madrid, Spain
    • Pesticide Residue Research Group, Department of Hydrogeology and Analytical Chemistry, University of Almería, Almería, Spain
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Correspondence to: A. R. Fernández-Alba, IMDEA – Agua (Instituto Madrileño De Estudios Avanzados – Agua), Parque Científico Tecnológico, University of Alcalá, 28805 Alcalá de Henares, Madrid, Spain.

E-mail: amadeo@ual.es

Abstract

RATIONALE

Poly(amidoamine) PAMAM dendrimers are highly water soluble and are used as flexible scaffolding or nanocontainers to conjugate, complex or encapsulate therapeutic drugs to overcome intrinsically weak characteristics such as solubilization in aqueous medium. To provide a reliable method for the quantitation of PAMAM dendrimers in aqueous medium, we report here a validation study which was developed in a complex wastewater matrix to evaluate the matrix effect in the electrospray ionization (ESI) source.

METHODS

PAMAM dendrimers (generations G0 to G3) were identified and quantitated in aqueous medium using liquid chromatography interfaced to a hybrid quadrupole/time-of-flight mass analyzer. This approach used the high resolving power of isotopic clusters and mass accuracy of the instrument, with especial attention to the tandem mass spectrometric (MS/MS) capabilities. The formation of multiply charged ions of PAMAM dendrimers in the ESI source and their later fragmentation allowed fragmentation paths to be determined and structural assignments to be made.

RESULTS

The analytical strategy allowed dendrimer identification with a high degree of confidence obtained by accurate mass and high resolution with mass errors below 5 ppm and 10 ppm in MS and MS/MS modes. The parameters of validation in spiked matrix were: limits of quantification in the range of 0.12 to 1.25 μM depending on the generation, linearity (R >0.996), repeatability (R.S.D. <6.7%) and reproducibility (R.S.D. <10.8%).

CONCLUSIONS

Accurate mass measurement, elemental composition, and charge state assignment through the resolution of isotopic clusters of product and precursor ions, confers enhanced confidence on PAMAM dendrimer characterization. This selectivity provided high discriminating capacity of PAMAM dendrimers against matrix interferences. Because of the reliable and reproducible quantitation by LC/ESI-QTOF-MS, analysis of PAMAM dendrimers in an aqueous matrix is feasible. Copyright © 2013 John Wiley & Sons, Ltd.

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