A liquid chromatography and tandem mass spectrometry method to determine 28 non-volatile drugs of abuse in exhaled breath

J Pharm Biomed Anal. 2018 Jan 30:148:251-258. doi: 10.1016/j.jpba.2017.10.003. Epub 2017 Oct 9.


Exhaled breath carries aerosol micro-particles containing nonvolatile organic substances. Recently, the analysis of drugs of abuse (DOA) have become of interest in exhaled breath particles (EBP). In this study, a liquid chromatography - tandem mass spectrometry (LC-MS/MS) method was developed and validated to analyze 28 DOA in 30L of EBP collected on a permeable polymer filter. After extraction, the chromatographic separation was achieved on a UPLC BEH phenyl column using a mobile phase consisting of methanol and water both containing 4mmol/L ammonium formate and 0.05% ammonia. The column temperature was set at 50°C and mobile phase flow rate 0.5mL/min in gradient mode with a total run time of 5min. The mass spectrometer was operated in positive electrospray ionization and selected reaction monitoring mode. Acquired limits of quantification were in the range of 1-66pg/filter for all substances except DM-tramadol. Excellent linearity over the concentration range from LLOQs - 15ng/filter with r2 values >0.99 and satisfactory recoveries (70-116% at 100pg/filter) were achieved. During method application a total 26 samples were analyzed of which 24 were found to be positive for 13 analytes. The highest amount was found for methadone (56ng/filter) and the lowest amount was found for the methadone metabolite EDDP (2pg/filter) in two different samples.

Keywords: Alternative matrix; Drugs of abuse; Exhaled breath; LC–MS/MS.

MeSH terms

  • Aerosols / chemistry*
  • Breath Tests / methods
  • Chromatography, High Pressure Liquid / methods
  • Exhalation / physiology
  • Humans
  • Illicit Drugs / analysis*
  • Illicit Drugs / chemistry*
  • Methadone / chemistry
  • Substance-Related Disorders / diagnosis
  • Tandem Mass Spectrometry / methods


  • Aerosols
  • Illicit Drugs
  • Methadone