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Catecholamine measurements As described before 15 , UPLC-MS/MS was used to analyze urinary levels of free biogenic monoamines (including catecholamines), and their metabolites were measured by 5 L of urine samples from frozen biobanked (-80C) random samples were thawed on ice and mixed with 50 L of deuterated internal standards (epinephrine-d6, norepinephrine-d6, dopamine-d4, metanephrine-d3, normetanephrine-d3, 4-hydroxy-3-methoxymandelic acid d3, 4-hydroxy-3-methoxyphenyl-d3-acetic-d2 acid, 5-hydroxyindole-4,6,7-d3-3-acetic-d2 acid) and 195 L of 0.2% formic acid in a 2 mL amber UPLC sample vial and the samples were analyzed on a Xevo TQ-S micro quadrupole mass spectrometer with an ESI ionization source, interfaced with Waters Acquity Class-H UPLC equipped with a quaternary pump system (Waters, MA)

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The Tobacco Institute was even created in this country, thanks to whose research the quality of the products has greatly improved