A test to detect opioid drugs in exhaled breath has been developed by engineers and physicians at the University of California – Davis. A breath test could be useful in caring for chronic pain patients as well as for checking for illegal drug use.
"There are a few ways we think this could impact on society," said Professor Cristina Davis, chair of the department of mechanical and aerospace engineering at UC Davis, who led the research along with Professor Michael Schivo from the UC Davis Medical Centre.
Doctors and nurses treating chronic pain may need to monitor patients to make sure they are taking their drugs correctly, that their prescribed drugs are being metabolized properly and that they are not taking additional medications. Blood tests are the gold standard: a reliable, non-invasive test would be a useful alternative.
For the test developed by post-doctoral researcher Eva Borras, Davis and colleagues, subjects breathe normally into a specialized collection device. Droplets in breath condense and are stored in a freezer until testing. Davis' lab uses mass spectrometry to identify compounds in the samples.
The researchers tested the technique in a small group of patients receiving infusions of pain medications including morphine and hydromorphone, or oral doses of oxycodone, at the UC Davis Medical Centre. They were therefore able to compare opioid metabolites in breath with both blood samples and the doses given to patients.
"We can see both the original drug and metabolites in exhaled breath," Davis said. Fully validating the breath test will require more data from larger groups of patients, she said. Davis' laboratory is working toward real-time, bedside testing.
Other authors on the paper include graduate student Andy Cheng, UC Davis forensic science programme; Ted Wun, department of internal medicine; Kristen Reese and Matthias Frank, Lawrence Livermore National Laboratory; and Michael Schivo, UC Davis School of Medicine and VA Northern California Health System.
Davis' laboratory is working on a variety of applications for detecting small amounts of chemicals, especially in air and exhaled breath. Other projects include diagnosing influenza in people and citrus greening disease in fruit trees.
The work was supported by grants from the UC Davis Medical Centre's Collaborative for Diagnostic Innovation, the US Department of Energy and the NIH.
Detecting opioids metabolites in exhaled breath condensate
Journal of Breath Research
Exhaled breath condensate (EBC) collection provides a promising matrix for bioanalysis of endogenous biomarkers of health and also for exogenous compounds like drugs. There is little information regarding drugs and their metabolites contained in breath, as well as their pharmacokinetics. In this present work, we use a simple and non-invasive technique to collect EBC from chronic pain patients using different analgesic opioid drugs to manage pain. Six patients received continuous infusion of morphine and hydromorphone intravenously (IV), together with other analgesic drugs (IV and orally). Repeated sampling of serum and EBC was done at two time points separated by 90 min. The EBC was collected using a glass tube surrounded by dry ice, and an ethanol solvent wash of the glass was performed after EBC extraction to retrieve the apolar compounds stuck to the glass surface. All samples were analyzed with liquid chromatography coupled to mass spectrometry (LC-MS/MS) to identify possible metabolites present in the sample, and to quantify the drugs being used. Several metabolites, such as normorphine (norM), norhydromorphone (norHM) and dihydromorphone (diHM) were detected in both fractions, while hydromorphone 3-glucuronide (HM 3G) was only detected in the solvent rinse fraction. Results were correlated to explain the pharmacokinetics of the main drugs administered. This pilot study presented promising correlations between drug concentrations in blood and breath at different time points for norM, norHM and HM 3G.
Eva Borras, Andy Cheng, Ted Wun, Kristen L Reese, Matthias Frank, Michael Schivo, Cristina E Davis