RAPID COMMUNICATIONS IN MASS SPECTROMETRY Rapid Commun. Mass Spectrom. 2006; 20: 61–68 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/rcm.2275 A longitudinal study of ethanol and acetaldehyde in the exhaled breath of healthy volunteers using selected-ion flow-tube mass spectrometry Claire Turner 1 * ,{ , Patrik S ˇ pane ˇl 2 and David Smith 3 1 Silsoe Research Institute, Wrest Park, Silsoe, Bedford MK45 4HS, UK 2 V. C ˇ erma ´k Laboratory, J. Heyrovsky ´ Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, Dolejs ˇkova 3, 182 23 Prague 8, Czech Republic 3 Institute for Science and Technology in Medicine, School of Medicine, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, UK Received 3 September 2005; Revised 3 November 2005; Accepted 3 November 2005 Selected-ion flow-tube mass spectrometry (SIFT-MS) has been used to monitor the volatile com- pounds in the exhaled breath of 30 volunteers (19 male, 11 female) over a 6-month period. Volun- teers provided breath samples each week between 8:45 and 13:00 (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ethanol and acetaldehyde, which were simultaneously quantified by SIFT-MS using H 3 O þ precursor ions. The mean ethanol level for all samples was 196 parts-per-billion (ppb) with a standard devia- tion of 244 ppb, and the range of values for breath samples analysed is 0 to 1663 ppb. The mean acetaldehyde level for all samples was 24 ppb with a standard deviation of 17 ppb, and the range of values for breath samples analysed is 0 to 104 ppb. Background (ambient air) levels of ethanol were around 50 ppb, whereas any background acetaldehyde was usually undetectable. Increased ethanol levels were observed if sweet drink/food had been consumed within the 2 h prior to pro- viding the breath samples, but no increase was apparent when alcohol had been consumed the pre- vious evening. The measured endogenous breath ethanol and acetaldehyde levels were not correlated. These data relating to healthy individuals are a prelude to using breath analysis for clin- ical diagnosis, for example, the recognition of bacterial overload in the gut (ethanol) or the possibly of detecting tumours in the body (acetaldehyde). Copyright # 2005 John Wiley & Sons, Ltd. Ethanol is one of the few breath metabolites routinely mea- sured, principally by law enforcement officers checking that it is below that permitted by law (in the UK 180 ppm, equiva- lent to a blood level of 0.8 g/L). However, the legal drink- drive limit is typically 1000 times that of the typical endogen- ously produced ethanol concentration measured in exhaled human breath. Endogenous ethanol in breath, i.e. that pro- duced within the body and unrelated to ingestion of alcohol, has previously been measured over 30 days in five human volunteers using selected-ion flow-tube mass spectrometry (SIFT-MS), and found to be between 0 and 380 parts-per- billion (ppb), 1 with mean values for each of the five volun- teers over the 30-day period ranging between 27 to 153 ppb. In the same study breath acetaldehyde was quantified simul- taneously, resulting in a mean level for the five volunteers between 2 and 5 ppb. The present work extends the earlier study 1 by studying the composition of exhaled breath in a larger cohort of 30 volunteers over an extended time period of 6 months (commonly termed a longitudinal study), and includes data from some volunteers who had ingested alcohol the previous day. The improved sensitivity of the SIFT-MS analytical instrument (see below) also allowed more accurate quanti- fication of acetaldehyde in the breath. We also briefly examine the role of mouth production of breath ethanol, and demonstrate that its level can be influenced by mouth flora and the consumption of sweet food or drink prior to sampling, although this will be the topic of a later detailed study. It has been known for decades that acetaldehyde is an intermediate in the metabolism of ethanol in the liver. 2 Ethanol is converted into acetaldehyde by the enzyme alcohol dehydrogenase, and the acetaldehyde is then converted into acetic acid by acetaldehyde dehydrogenase. 3 Acetaldehyde is a highly toxic compound, with a 50% lethal dose (LD 50 ) concentration in rats that is about ten times lower than that for ethanol. 4 Hence it needs to be removed from the Copyright # 2005 John Wiley & Sons, Ltd. *Correspondence to: C. Turner, Department of Analytical Science and Informatics, Cranfield University, Silsoe, Bedford MK45 4DT, UK. E-mail: c.turner@cranfield.ac.uk { Present address: Department of Analytical Science and Informatics, Cranfield University, Silsoe, Bedford MK45 4DT, UK. Contract/grant sponsor: Silsoe Research Institute’s Central Strategic Grant from the BBSRC.