title: Determination of 4-aminophenol in a pharmaceutical formulation using surface enhanced Raman scattering: from development to method validation.
abstract: A surface enhanced Raman scattering (SERS) method able to quantify 4-aminophenol in a pharmaceutical formulation based on acetaminophen, also called paracetamol, was developed and, for the first time, successfully validated. In this context, silver nanoparticles were synthesized according to the method described by Lee-Meisel and used as SERS substrate. The repeatability of the silver colloid synthesis was tested using different methods to characterize the size and the zeta potential of silver nanoparticles freshly synthesized. To optimize the SERS samples preparation, a design of experiments implicating concentrations of citrate-reduced silver nanoparticles and aggregating agent was performed in order to maximize the Raman signal enhancement. Finally, an approach based on tolerance intervals and accuracy profiles was applied in order to thoroughly validate the method in a range of concentrations comprised from 3 to 15 µg mL(-1) using normalized band intensities. The standard addition method was selected as method calibration. Therefore, measurements were carried out on 4-aminophenol spiked solutions of the pharmaceutical formulation. Despite the well-known stability and reproducibility problems of SERS, the validation was performed using two operators and five batches of nanoparticles, one for each validation day.
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, B-4000 Liege, Belgium. Electronic address: cdebleye@ulg.ac.be.
authors.forename: C
authors.initials: C
authors.lastname: De Bleye
authors.forename: E
authors.initials: E
authors.lastname: Dumont
authors.forename: E
authors.initials: E
authors.lastname: Rozet
authors.forename: P-Y
authors.initials: PY
authors.lastname: Sacré
authors.forename: P-F
authors.initials: PF
authors.lastname: Chavez
authors.forename: L
authors.initials: L
authors.lastname: Netchacovitch
authors.forename: G
authors.initials: G
authors.lastname: Piel
authors.forename: Ph
authors.initials: P
authors.lastname: Hubert
authors.forename: E
authors.initials: E
authors.lastname: Ziemons
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D000627:Aminophenols / Q000032:analysis*; D002138:Calibration; D004340:Drug Contamination; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D011208:Powders; D015203:Reproducibility of Results; D012834:Silver / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013499:Surface Properties
chemical_list: D000627:Aminophenols; D011208:Powders; D000082:Acetaminophen; D012834:Silver; C026729:4-aminophenol
keywords: 4-Aminophenol; Accuracy profile; Pharmaceutical matrix; Quantitative determination; Surface enhanced Raman scattering; Validation