title: Quantitative determination of poly(amidoamine) dendrimers in urine by liquid chromatography/electrospray ionization hybrid quadrupole linear ion trap mass spectrometry.
abstract: BACKGROUND
  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∙10-4to 5∙10-2mmol.L-1), and sensitivity within the micromolar range. The detection limit values were above 1∙10-4mmol.L-1in 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.
authors.affiliation: 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; IMDEA-Water (Madrid Institute for Advanced Studies-Water), Parque Científico Tecnológico, University of Alcalá, 28805, Alcalá de Henares, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Uclés
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Martínez Bueno
authors.forename: Maria Malgorzata
authors.initials: MM
authors.lastname: Ulaszewska
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Hernando
authors.forename: Carmen
authors.initials: C
authors.lastname: Ferrer
authors.forename: Amadeo R
authors.initials: AR
authors.lastname: Fernández-Alba