Advanced analytical approach for the determination of NDELA and twelve other N-nitrosamines in cosmetic products

Planinšek Parfant, Timeja (author), Roškar, Robert (author)

N-nitrosamines (NA) are probable human carcinogens that are prohibited in cosmetic products (CP). Nevertheless, certain CP ingredients, such as amines and nitrosating agents, can unintentionally lead to NA formation, with N-nitrosodiethanolamine (NDELA) being the most frequently detected. Regulatory authorities have therefore set a limit of 50 μg/kg for total NA content in CPs. Due to the lack of analytical methods capable of simultaneously quantifying NDELA alongside other less polar NAs, this study presents a novel approach combining selective two-step sample preparation with liquid chromatography coupled to high-resolution mass spectrometry for the simultaneous determination of 13 NAs in various CPs. The proposed solvent extraction with dichloromethane followed by solid-phase extraction using Strata X-C cartridges proved highly effective for both matrix removal and selective NA extraction from the complex composition of CPs. The method was fully validated and showed excellent specificity, linearity, accuracy, and precision across a wide concentration range, including at the regulatory limit. Application of the method to 53 commercially available CPs, all containing at least one known NA precursor or nitrosating agent, showed the presence of three different NAs in 28.3 % of samples. NDELA was the most prevalent, and 15.1 % of CPs, mainly shampoos, exceeded the regulatory limit (between 50.5 and 159.5 μg/kg). The wide applicability and high sensitivity of this robust and reliable method make it a valuable tool for quality control of multiple NAs in CPs, including the most challenging compounds such as NDELA. This ensures regulatory compliance, improves CP safety, and thereby reduces the risk to human health.

• Language: English
• Keywords: N-nitrosamines, N-nitrosodiethanolamine, cosmetics, high-resolution mass spectrometry, solid-phase extraction, genotoxic impurities
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 11 str.
• Numbering: Vol. 218, art. 115521
• PID: 20.500.12556/RUL-174746
• UDC: 616-006:665.58
• ISSN on article: 0026-265X
• DOI: 10.1016/j.microc.2025.115521
• COBISS.SI-ID: 252434179
• Publication date in RUL: 09.10.2025

Record is a part of a journal

• Title: Microchemical journal
• Shortened title: Mirochem. j.
• Publisher: Elsevier
• ISSN: 0026-265X
• COBISS.SI-ID: 25947648

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: N-nitrozamini, N-nitrozodietanolamin, kozmetika, visokoločljivostna masna spektrometrija, ekstrakcija v trdni fazi, genotoksične nečistoče, kozmetični izdelki, karcinogeni, masna spektrometrija, genotoksičnost

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0189
• Name: Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih