In yesterday’s session “Moving Beyond Immunoassays for the Poisoned Patient: Analytical Approaches and Interactive Case Studies,” Amitava Dasgupta, PhD, and Kara Lynch, PhD, dealt with this conundrum of interfacing with clinicians.

Dasgupta discussed ways to empower clinicians who recognize the clinical signs of a drug overdose but then receive conflicting drug screen results in which all drug components are negative. He explained a clinical algorithm that aids in guiding further, more defined drug testing when presented with conflicting clinical and testing information. The algorithm guides clinicians to order appropriate tests depending on the demographic of the patient. This allows for more focused testing rather than a broad spectrum approach, saving time and money. For example, Dasgupta discussed an example where the algorithm suggested ordering a drug confirmation panel specific for synthetic cannabinoids because the patient in question was a known marijuana user.

Kara Lynch, PhD, shared her perspective on current trends in immunoassay drug testing and made a case for why traditional immunoassay drug screens may no longer be appropriate as part of the drug testing algorithm. Current immunoassay drug screens contain a set number of analyte components, she noted. But these drug screens have not changed much in the past 20 years.

Historically, a completely negative drug screen would provide confidence to both laboratory personnel and clinicians that the patient wasn’t using any drugs. This is not the case anymore, Lynch emphasized. Many of these assays are designed to detect a structural family of drugs in order to capture more positive results. A good example is opiates, where antibodies may be raised against a single drug like morphine, but can also cross react with codeine and heroin metabolites. Lynch explained the problem with this approach: Many opiate-like drugs are structurally too dissimilar to morphine to be detected in that screen.

Lynch suggested that mass spectrometry-based screening may provide the comprehensive testing necessary to detect more exotic drugs not currently detected using most immunoassay platforms. She used compelling interactive case studies, one of which was particularly intriguing.

She described a 27-year-old male and a 37-year-old female who presented at an emergency department with extremity weakness. Further investigation revealed that they “fell asleep” after using consuming alcohol, cocaine, and Xanax. Both patients were found to have elevated troponins and rhabdomyolyses, both of which were inconsistent with the claimed drugs used.

Sample acquisition by mass spectrometry that Kara described identified metabolites of cocaine which was expected. No alprazolam (Xanax) or metabolites of alprazolam were identified. Fentanyl, norfentanyl (fentanyl metabolite) and etizolam (a potent benzodiazepine analog) were identified, however. This identification led to an investigation of the “Xanax tablets” that were used by the patients, which were found to contain no alprazolam, but contained fentanyl and etizolam.

Further overdose cases and even four deaths were found to be associated with these fake Xanax tablets. Early identification of these compounds using mass spectrometry and subsequent alerts to the local community likely led to far fewer overdoses and deaths from using these potent substances.

As the number of designer drugs grows, we will be faced with ever more challenging overdose cases and the drug testing needed to treat them. Fortunately, we can learn from experts like Dasgupta and Lynch at the AACC Annual Scientific Meeting, who have helped us identify the current barriers and solutions needed to stay one step ahead of this tangled mess.