Methods for Pharmaceutical and Illicit Drug Analysis

Pharmaceutical and illicit drugs are highly regulated classes of compounds. Despite regulation efforts, people all over the world consume drugs of unknown composition each day, causing adverse health outcomes. Analytical testing is a crucial aspect of ensuring drug safety, requiring both the technical capacity for testing and the systems in place for results of analysis to be disseminated accurately and efficiently to those who need them. My thesis work focuses on the analysis of both pharmaceutical and illicit drugs that slip through the cracks of regulation. Analysis techniques include high-performance liquid chromatography (HPLC), liquid chromatography tandem mass-spectrometry (LC-MS/MS), and immunoassay test strips. My work has also focused on the establishment and administration of community-based collaborations for ensuring the quality of drugs.

Through my work on illicit drugs, I sought to determine which drugs are being missed with existing drug checking techniques. Chapters 2 and 3 focus on fentanyl test strips (FTS), which are lateral flow immunoassays used for the off-label purpose of detecting fentanyl in street drugs as a means of harm reduction. In chapter 2, I assess the ability of 2 popular brands of FTS to detect 217 fentanyl analogs and fentanyl-related compounds and correlate reactivity with chemical structure to determine which modifications are in the “blind spots” of each brand’s FTS. This work identified 80 fentanyl analogs that were detectable by only one brand but not the other and suggests using two brands of FTS for drug checking could be the best policy for ensuring an analog is not missed in drug checking. In chapter 3, I describe the need and plans for a community-based collaboration to assess the quality of FTS. As FTS have grown in popularity, concerns over lot-to-lot variation and brand-to-brand variation among harm reduction organizations and people who use drugs have increased, as FTS for drug checking are not monitored by any regulatory agencies in North America. This collaboration seeks to prevent quality issues that arise from high demand for an unregulated product which were seen with a similar technology, malaria rapid diagnostic tests, in the early 2000’s. In chapter 4, I describe the development and validation of an LC-MS/MS method targeting 26 fentanyl analogs, synthetic opioids, and emergent drugs of concern. I used this method to screen 79 street drug samples collected in Chicago, IL that had been previously analyzed on two other LC-MS/MS methods to determine if we had missed drugs of concern in the original analyses. Results of this work revealed that over half of these samples contained high concentrations of xylazine, an emergent threat that has been associated with hundreds of overdose deaths in Chicago. The high sensitivity of this method also allowed for the detection of trace contaminants which likely came from incidental contact during the illicit manufacture, storage, or distribution of samples and which could provide powerful information about what substances are present in the illicit supply chain.

Chapters 5 and 6 focus on detecting substandard and falsified pharmaceutical products (SFPs) in low- and middle-income countries (LMICs) through the Distributed Pharmaceutical Analysis Laboratory (DPAL). Chapter 5 describes results of analysis for 824 antibiotics collected in Western Kenya between 2020-2021. Through this analysis, 37 samples that failed analysis were detected including amoxicillin and amoxicillin-clavulanate capsules, ciprofloxacin tables, and ceftriaxone powder for injection. This work revealed limitations in DPAL data and communication management strategies that prevented timely analysis of hundreds of medicines. A plan to address these shortcomings is described in chapter 6, which proposes a blockchain ledger for managing the DPAL workflow.