Analysis of Alkaloids in Areca Nut-Containing Products by Liquid Chromatography-Tandem Mass Spectrometry

Vipin Jain, Apurva Garg, Mark Parascandola, Pankaj Chaturvedi, Samir S. Khariwala, Irina Stepanov

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16 Scopus citations


Chewing of areca nut in different forms such as betel quid or commercially produced pan masala and gutkha is common practice in the Indian subcontinent and many parts of Asia and is associated with a variety of negative health outcomes, particularly oral and esophageal cancers. Areca nut-specific alkaloids arecoline, arecaidine, guvacoline, and guvacine have been implicated in both the abuse liability and the carcinogenicity of the areca nut. Therefore, variations in the levels of areca alkaloids could potentially contribute to variations in addictive and carcinogenic potential across areca nut-containing products. Here, we developed an accurate and robust liquid chromatography-tandem mass-spectrometry (LC-MS/MS) method for simultaneous quantitation of all four areca alkaloids and applied this method to the analysis of a range of products obtained from India, China, and the United States. The results of the analyses revealed substantial variations in the levels of alkaloids across the tested products, with guvacine being the most abundant (1.39-8.16 mg/g), followed by arecoline (0.64-2.22 mg/g), arecaidine (0.14-1.70 mg/g), and guvacoline (0.17-0.99 mg/g). Substantial differences in the relative contribution of individual alkaloids to the total alkaloid content were also observed among the different products. Our results highlight the need for systematic surveillance of constituent levels in areca nut-containing products and a better understanding of the relationship between the chemical profile and the harmful potential of these products.

Original languageEnglish (US)
Pages (from-to)1977-1983
Number of pages7
JournalJournal of agricultural and food chemistry
Issue number9
StatePublished - Mar 8 2017

Bibliographical note

Funding Information:
This study was supported by Contract HHSN261201200392P and Grant CA180880 from the National Cancer Institute, Grant K23DE023572 from the National Institute of Dental and Craniofacial Research, and by startup funds to I.S. from the Masonic Cancer Center. LC?MS/MS was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, supported in part by Grant CA-77598 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank Xun Ming and Peter Villalta for their help with the mass spectrometry analysis and Bob Carlson for editorial assistance.


  • LC−MS/MS
  • areca nut
  • arecaidine
  • arecoline
  • guvacine
  • guvacoline

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