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

Authors

  • Ana Uclés,

    1. Pesticide Residues Research Group, European Union Reference Laboratory (EURL), Department of Chemistry and Physics, University of Almería, Almería, Spain
    2. IMDEA-Water (Madrid Institute for Advanced Studies-Water), Parque Científico Tecnológico, University of Alcalá, Alcalá de Henares, Madrid, Spain
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  • María Jesús Martínez Bueno,

    1. Pesticide Residues Research Group, European Union Reference Laboratory (EURL), Department of Chemistry and Physics, University of Almería, Almería, Spain
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  • Maria Malgorzata Ulaszewska,

    1. IMDEA-Water (Madrid Institute for Advanced Studies-Water), Parque Científico Tecnológico, University of Alcalá, Alcalá de Henares, Madrid, Spain
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  • María Dolores Hernando,

    1. National Institute for Agricultural and Food Research and Technology – INIA, Madrid, Spain
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  • Carmen Ferrer,

    1. Pesticide Residues Research Group, European Union Reference Laboratory (EURL), Department of Chemistry and Physics, University of Almería, Almería, Spain
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  • Amadeo R. Fernández-Alba

    Corresponding author
    1. Pesticide Residues Research Group, European Union Reference Laboratory (EURL), Department of Chemistry and Physics, University of Almería, Almería, Spain
    • IMDEA-Water (Madrid Institute for Advanced Studies-Water), Parque Científico Tecnológico, University of Alcalá, Alcalá de Henares, Madrid, Spain
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Correspondence to: A. R. Fernández-Alba, Pesticide Residues Research Group, European Union Reference Laboratory (EURL), Department of Chemistry and Physics, University of Almería, 04120 La Cañada de San Urbano, Almería, Spain.

E-mail: amadeo@ual.es

Abstract

RATIONALE

Dendrimer nanocarriers have become of increasing interest in the field of biomedicine for their drug delivery potential. Surface modifications and optimized nanosize control are the strategies being followed to enhance drug delivery efficacy and renal clearance, especially for dendrimers of a lower generation number. The aim of this study was the development and performance evaluation of an analytical method for the quantitative determination of polyamidoamine (PAMAM) dendrimers in urine.

METHODS

PAMAM dendrimers (generations G0 to G3) were analyzed using liquid chromatography/electrospray ionization hybrid quadrupole linear ion trap mass spectrometry (LC/ESI-QqLIT-MS). Quantitative analysis was performed in selected reaction monitoring (SRM) mode. To confer a higher degree of confidence on the identification of PAMAM dendrimers, an SRM scan and collision-induced dissociation (CID), as a dependent scan, were performed in one single run using the information-dependent acquisition (IDA) mode.

RESULTS

The LC/ESI-QqLIT-MS method, in SRM mode, allowed quantitative determination in urine matrix with good repeatability and reproducibility (relative standard deviation (R.S.D.) from 2 to 15%), linearity (R >0.99) over the concentration range (6∙10–4 to 5∙10–2 mmol.L–1), and sensitivity within the micromolar range. The detection limit values were above 1∙10–4 mmol.L–1 in both solvent and urine, for the generations studied.

CONCLUSIONS

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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