Affiliations 

  • 1 Centre for Sustainable Nanomaterials, Ibnu Sina Institute for Scientific and Industrial Research, Universiti Teknologi Malaysia UTM, Johor Bahru, Johor 81310, Malaysia; Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia UTM, Johor Bahru, Johor 81310, Malaysia
  • 2 Centre for Sustainable Nanomaterials, Ibnu Sina Institute for Scientific and Industrial Research, Universiti Teknologi Malaysia UTM, Johor Bahru, Johor 81310, Malaysia; Australian Centre for Research on Separation Science, School of Physical Sciences - Chemistry, University of Tasmania, Hobart, Tasmania 7001, Australia
  • 3 Allied Chemists Laboratory Sdn Bhd, 1 & 3, Jalan Gemilang 7, Taman Perindustrian Cemerlang, Johor Bahru, Johor 81800, Malaysia
  • 4 Centre for Sustainable Nanomaterials, Ibnu Sina Institute for Scientific and Industrial Research, Universiti Teknologi Malaysia UTM, Johor Bahru, Johor 81310, Malaysia; Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia UTM, Johor Bahru, Johor 81310, Malaysia. Electronic address: hhsee@utm.my
J Chromatogr A, 2022 Dec 06;1685:463605.
PMID: 36375217 DOI: 10.1016/j.chroma.2022.463605

Abstract

A new dispersive inclusion complex microextraction (DICM) approach coupled with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for the determination of n-nitrosamine impurities in different medicinal products is demonstrated for the first time. The proposed DICM procedures consist of a dispersive liquid phase microextraction steps employing cyclodextrin as an inclusion complex agent to extract n-nitrosamines namely N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodiisopropylamine (NDIPA), N-ethyl-N-nitrosoisopropylamine (NEIPA) and N-nitroso-di-n-butylamine (NDBA) present in the medicinal products. The sample solutions were prepared by mixing 5% (m/v) NaCl solution with 1.5 mM β-cyclodextrin and 20 mM sodium dodecyl sulphate to form a stable inclusion complex and subsequently extracted into dichloromethane as an extraction solvent. The enriched solution was reconstituted into aqueous solution prior to UPLC-MS/MS analysis. The method showed good linearity in the range of 0.036-1 ng/mL with a correlation coefficient of at least 0.995, acceptable reproducibility (RSD 0.5-5.8%, n=5), low limits of detection (0.011-0.018 ng/mL), and satisfactory relative recoveries (96-105%). The results obtained were found to be at least 10-fold more sensitive comparable to those obtained using validated direct sample dissolutions coupled with UPLC-MS/MS approach.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.