Rapid Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method to Measure Cannabinoids in Bronchoalveolar-Lavage Fluid of Patients with e-Cigarette, or Vaping, Product Use-Associated Lung Injury

In 2019, the Centers for Disease Control and Prevention responded to an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). Bronchoalveolar-lavage (BAL) fluid from EVALI patients was available for analysis to investigate a range of potential toxicants that might be present at the presumed site of lung injury. Our laboratory developed and validated a novel method to measure cannabinoids and their metabolites in BAL fluid to aid in the investigation of the toxicants that might be the cause of EVALI. In this paper, we describe a sensitive liquid chromatography-tandem mass spectrometry method to measure the following six cannabinoids: Delta(9)-tetrahydrocannabinol (THC), THC metabolites 11-nor-9-carboxy-THC and 11-hydroxy-THC, cannabinol, cannabidiol (CBD), and CBD metabolite 7-nor-7-carboxycannabidiol. Cannabinoids were extracted from BAL fluid using solid-phase extraction. Accuracy, precision, stability, and limits of detection were determined from replicate analyses of spiked BAL pools. The lower limits of detection ranged from 0.019 to 0.153 ng/mL for a sample volume of 150 mu L. Overall accuracy ranged from 71.0 to 100.8%. Within-run imprecision (measured by the coefficient of variation) was below 8%, and between-run imprecision was below 21% for all analytes and concentrations tested. The method was applied to samples from 59 EVALI case patients. We identified THC, CBD, or their metabolites in 76% of EVALI patient samples. These findings support previous evidence that THC-containing products played a major role in the EVALI outbreak and help to inform public health recommendations.