title: Development of a quantitative approach using surface-enhanced Raman chemical imaging: first step for the determination of an impurity in a pharmaceutical model.
abstract: This publication reports, for the first time, the development of a quantitative approach using surface-enhanced Raman chemical imaging (SER-CI). A pharmaceutical model presented as tablets based on paracetamol, which is the most sold drug around the world, was used to develop this approach. 4-Aminophenol is the main impurity of paracetamol and is actively researched in pharmaceutical formulations because of its toxicity. As its concentration is generally very low (<0.1%, w/w), conventional Raman chemical imaging cannot be used. In this context, a SER-CI method was developed to quantify 4-aminophenol assessing a limit of quantification below its limit of specification of 1000 ppm. Citrate-reduced silver nanoparticles were used as SERS substrate and these nanoparticles were functionalized using 1-butanethiol. Different ways to cover the tablets surface by butanethiol-functionalized silver nanoparticles were tested and a homogeneity study of the silver nanoparticles covering was realized. This homogeneity study was performed in order to choose the best way to cover the surface of tablets by silver colloid. Afterwards, the optimization of the SER-CI approach was necessary and different spectral intensity normalizations were tested. Finally, a quantitative approach using SER-CI was developed enabling to quantify 4-aminophenol from 0.025% to 0.2% in paracetamol tablets. This quantitative approach was tested on two different series of tablets using different batches of silver nanoparticles.
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.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, B-4000 Liege, Belgium.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Sacré
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, B-4000 Liege, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Dumont
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, B-4000 Liege, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Netchacovitch
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, B-4000 Liege, Belgium.
authors.forename: P-F
authors.initials: PF
authors.lastname: Chavez
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Pharmaceutical Technology, CHU, B36, B-4000 Liege, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Piel
authors.affiliation: Arlenda S.A. Avenue de l'Hôpital, 1, B-4000 Liege, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Lebrun
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, B-4000 Liege, Belgium.
authors.forename: Ph
authors.initials: P
authors.lastname: Hubert
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, B-4000 Liege, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Ziemons
mesh_terms: D000082:Acetaminophen / Q000032:analysis / Q000737:chemistry* / Q000592:standards; D000627:Aminophenols / Q000032:analysis*; D057230:Limit of Detection; D053768:Metal Nanoparticles; D012834:Silver / Q000737:chemistry; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013607:Tablets
chemical_list: D000627:Aminophenols; D013438:Sulfhydryl Compounds; D013607:Tablets; D000082:Acetaminophen; D012834:Silver; C025540:n-butyl mercaptan; C026729:4-aminophenol
keywords: Chemical imaging; Pharmaceutical model; Quantitative approach; Silver colloid covering; Surface-enhanced Raman scattering