Abstract
BackgroundBiomarkers 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.FindingsThis 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%.ConclusionThe 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.
Highlights
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 gas phase, tobacco smoke toxicant acrolein [CAS:107-02-8] (Figure 1A) has been identified by the World Health Organization (WHO) study group on Tobacco Product Regulation (TobReg) as a major contributor to smoke toxicity [4]. This evaluation was based on the concentration of acrolein in smoke and its toxicity potency factor, established using various models. 3-hydroxypropylmercapturic acid (3HPMA) is the major urinary metabolite of acrolein (Figure 1B) [5], and it can be quantified using liquid chromatography-mass spectrometry (LC-MS) based methods [3,5]
A study conducted by Biber and colleagues on a common set of urinary and plasma samples comparing nicotine and cotinine data from eleven laboratories concluded that individual values could vary significantly between laboratories [6]
Summary
The results from this first inter-laboratory comparison for the measurement of 3-HPMA in urine demonstrate a reasonably good consensus between laboratories. 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
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