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An inter-laboratory comparison of urinary 3-hydroxypropylmercapturic acid measurement demonstrates good reproducibility between laboratories

Emmanuel Minet1*, Graham Errington1, Gerhard Scherer2, Kirk Newland3, Mehran Sharifi4, Brian Bailey5, Mike McEwan1 and Francis Cheung1

Author Affiliations

1 British American Tobacco, Group Research and Development, Regents Park Road, Southampton, SO15 8TL, UK

2 Analytisch-Biologisches Forschungslabor GmbH, Goethestrasse 20, 80336 Muenchen, Germany

3 Celerion, 621 Rose Street, Lincoln, NE 68502, USA

4 Labstat International Inc., 262 Manitou Drive, Kitchener, Ontario N2C 1L3, Canada

5 Covance Laboratories Ltd, Otley Road, Harrogate, HG3 1PY, UK

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BMC Research Notes 2011, 4:391  doi:10.1186/1756-0500-4-391

Published: 10 October 2011



Biomarkers have been used extensively in clinical studies to assess toxicant exposure in smokers and non-smokers and have recently been used in the evaluation of novel tobacco products. The urinary metabolite 3-HPMA, a metabolite of the major tobacco smoke toxicity contributor acrolein, is one example of a biomarker used to measure exposure to tobacco smoke. A number of laboratories have developed liquid chromatography with tandem mass spectrometry (LC-MS/MS) based methods to measure urinary 3-HPMA; however, it is unclear to what extent the data obtained by these different laboratories are comparable.


This report describes an inter-laboratory comparison carried out to evaluate the comparability of 3-HPMA measurement between four laboratories. A common set of spiked and authentic smoker and non-smoker urine samples were used. Each laboratory used their in-house LC-MS/MS method and a common internal standard. A comparison of the repeatability ('r'), reproducibility ('R'), and coefficient of variation for 3-HPMA demonstrated that within-laboratory variation was consistently lower than between-laboratory variation. The average inter-laboratory coefficient of variation was 7% for fortified urine samples and 16.2% for authentic urine samples. Together, this represents an inter-laboratory variation of 12.2%.


The results from this first inter-laboratory comparison for the measurement of 3-HPMA in urine demonstrate a reasonably good consensus between laboratories. However, some consistent measurement biases were still observed between laboratories, suggesting that additional work may be required to further reduce the inter-laboratory coefficient of variation.