Simultaneous analysis of urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N'-nitrosonornicotine, and cotinine by liquid chromatography-tandem mass-spectrometry.

Biomarkers of exposure to harmful tobacco constituents are key tools for identifying individuals at risk and developing interventions and tobacco control measures. However, tobacco biomarker studies are scarce in many parts of the world with high prevalence of tobacco use. Our goal was to establish a robust method for simultaneous analysis of urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N'-nitrosonornicotine (NNN), and cotinine at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) in Mumbai, India. These biomarkers are validated measures of exposure to the carcinogenic tobacco nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and NNN and the addictive alkaloid nicotine, respectively. The established method is characterized by excellent accuracy, linearity, and precision, and was successfully applied to the analysis of 15 smokeless tobacco (SLT) users and 15 non-users of tobacco recruited in Mumbai. This is the first report of establishment of such procedure in a laboratory in India, which offers the first in-country capacity for research on tobacco carcinogenesis in Indian SLT users.

Observed Circumvention of the Gutka Smokeless Tobacco Ban in Mumbai, India.

OBJECTIVES: Gutka is industrially manufactured in India and some Indian states have instituted bans on the sale of manufactured gutka as a public health initiative. We explored whether gutka was still available for purchase after the ban and also sought to observe methods of ban circumvention. METHODS: We visited 5 different markets at different locations separated by at least 15-20 km around the Mumbai Metropolitan Region (MMR) area, consisting of Mumbai and its satellite towns in Maharashtra, India during August- September, 2019. In each location, purveyors were queried as to the availability of gutka. RESULTS: Tobacco purchases were made in 5 locations/sections of MMR. At all markets, banned gutka was not displayed , and could only be purchased after requesting from the shopkeeper. Three methods of ban circumvention were observed: (1) packages marked 'export only'; (2) use of twin packaging in which pan masala and tobacco are sold together for immediate mixing to create gutka; and, (3) non-descript packaging without mention of 'gutka'. CONCLUSIONS: Although not readily displayed in shops, gutka is readily available in MMR, despite a statewide ban in Maharashtra. Marketers have used multiple methods to circumvent the statewide gutka ban.

Azine-Hydrazone Tautomerism of Guanylhydrazones: Evidence for the Preference Toward the Azine Tautomer.

Guanylhydrazones have been known for a long time and have wide applications in organic synthesis, medicinal chemistry, and material science; however, little attention has been paid toward their electronic and structural properties. Quantum chemical analysis on several therapeutically important guanylhydrazones indicated that all of them prefer the azine tautomeric state (by about 3-12 kcal/mol). A set of simple and conjugated azines were designed using quantum chemical methods, whose tautomeric preference toward the azine tautomer is in the range of 3-8 kcal/mol. Twenty new azines were synthesized and isolated in their neutral state. Variable temperature NMR study suggests existence of the azine tautomer even at higher temperatures with no traces of the hydrazone tautomer. The crystal structures of two representative compounds confirmed that the title compounds prefer to exist in their azine tautomeric form.