title: Development of a new sodium diclofenac certified reference material using the mass balance approach and ¹H qNMR to determine the certified property value.
abstract: Certified reference materials (CRMs) are essential tools to guarantee the metrological traceability of measurement results to the International System of Units (SI), which means the accuracy and comparability of results over time and space. In the pharmaceutical area, only a few CRMs are available and the use of (non-certified) reference materials is a much more common practice. In this paper, the studies on a new candidate CRM of sodium diclofenac based on the ISO Guides 34:2009 and 35:2005 are described. The project steps included characterization, homogeneity test, stability studies, and uncertainties estimation. In the characterization, the mass fractions of organic, inorganic, and volatile impurities were determined, and the results were cross-checked by independent reference methods or interlaboratorial study. The API mass fraction was calculated by mass balance and cross-checked by quantitative proton nuclear magnetic resonance (¹H qNMR). The paper also presents a Monte Carlo simulation to estimate the measurement uncertainty as an approach to validate the GUM results in ¹H qNMR. The homogeneity between batch units was verified, and the candidate CRM stability under transport and storage conditions was evaluated in short- and long-term stability studies. The CRM certified property value and corresponding expanded uncertainty, obtained from the combined standard uncertainty multiplied by the coverage factor (k=2), for a confidence level of 95%, was (999.76+0.10) mg g⁻¹.
authors.affiliation: National Institute of Metrology, Quality, and Technology (Inmetro), Chemical Metrology Division (Dquim), Av. Nossa Senhora das Graças, 50, Xerém, 25250-020 Rio de Janeiro, RJ, Brazil. Electronic address: rnogueira@inmetro.gov.br.
authors.forename: Raquel
authors.initials: R
authors.lastname: Nogueira
authors.affiliation: National Institute of Metrology, Quality, and Technology (Inmetro), Chemical Metrology Division (Dquim), Av. Nossa Senhora das Graças, 50, Xerém, 25250-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Garrido
authors.affiliation: Rio de Janeiro Federal University, Natural Products Research Center (NPPN), Brazil.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Borges
authors.affiliation: National Institute of Metrology, Quality, and Technology (Inmetro), Chemical Metrology Division (Dquim), Av. Nossa Senhora das Graças, 50, Xerém, 25250-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Gisele E B
authors.initials: GE
authors.lastname: Silva
authors.affiliation: National Institute of Metrology, Quality, and Technology (Inmetro), Chemical Metrology Division (Dquim), Av. Nossa Senhora das Graças, 50, Xerém, 25250-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Suzane M
authors.initials: SM
authors.lastname: Queiroz
authors.affiliation: National Institute of Metrology, Quality, and Technology (Inmetro), Chemical Metrology Division (Dquim), Av. Nossa Senhora das Graças, 50, Xerém, 25250-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Valnei S
authors.initials: VS
authors.lastname: Cunha
mesh_terms: D001938:Brazil; D002851:Chromatography, High Pressure Liquid; D004008:Diclofenac / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification / Q000592:standards; D004340:Drug Contamination; D004355:Drug Stability; D004356:Drug Storage; D017408:Guidelines as Topic; D007394:International System of Units; D057230:Limit of Detection; D008958:Models, Molecular; D009010:Monte Carlo Method; D066244:Proton Magnetic Resonance Spectroscopy; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical; D014186:Transportation; D035501:Uncertainty
chemical_list: D004008:Diclofenac