CORESTA Congress, Kunming, 2018, Smoke Science/Product Technology Groups, ST 59

An inter-laboratory comparison study focused on the determination of total NNAL in human urine

(1) Celerion Inc., Lincoln, NE, U.S.A.; (2) ABF GmbH, Planegg, Germany; (3) University of Minnesota Cancer Center, Minneapolis, MN, U.S.A.; (4) Reemtsma Cigarettenfabriken GmbH, Imperial Brands plc, Hamburg, Germany; (5) RAI Services Company, Winston-Salem, NC, U.S.A.

In an ongoing effort to fulfil the second objective of the CORESTA Biomarker Sub-Group, periodic inter-laboratory comparison studies have been performed to evaluate the consistency of the quantitation for various harmful or potentially harmful exposure markers. To further this objective an evaluation of the measures of total NNAL was conducted. 4-Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is the stable carbonyl reduced butanol metabolite of 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK has been identified as carcinogenic to humans by the International Agency for Research on Cancer. The measurement of total NNAL has been established as an acceptable biomarker to assess NNK exposure.

The inter-laboratory testing data provided by four separate laboratories was evaluated for consistency of quantitation. The initial results confirmed an analytically significant bias between the laboratories when quantitation was performed with standard calibrators prepared separately by each laboratory. Quality control samples prepared by supplementation with known amounts of the aglycone metabolite only showed a similar level of bias (35 %) to the multiple lots of urine collected from consented smokers that contain both the aglycone and glucuronide metabolites of NNAL (41 %). Comparability between the laboratories however was demonstrated when a uniform set of calibrators, which had been provided to each laboratory with the test samples, were used for quantitation.

The inter-laboratory comparison study effectively demonstrated the importance of such exercises to ensure the comparability of results provided by laboratories performing tobacco related research and to highlight the importance of the characterization and sourcing of quality reference materials to ensure comparability of results.