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Cigarettes and other products containing nicotine (NIC) remain a significant public health issue, with well-characterized harmful effects on the respiratory, cardiovascular, and other organ systems. (1) In addition to traditional [...], Context.--Consequences related to nicotine (NIC) use remain a major health concern, leading to demand for testing to detect NIC, metabolites such as cotinine (COT), and related tobacco alkaloids, including anabasine (ANAB). NIC-related testing is not standardized among laboratories, nor are there clinical or regulatory guidelines to inform decisions such as appropriate screening cutoffs or limits of quantitation. Objective.--To evaluate analytical performance and reporting practices of laboratories that perform NIC-related testing by reviewing participant responses to the Nicotine and Tobacco Alkaloid (NTA) Proficiency Testing Survey. Design.--NTA results were retrieved from 2017 (the first year of the survey) through 2020. Survey participants, methodologies, and results were evaluated for all analytes, and simulated grading was performed for COT. Additional data, including limits of quantitation, qualitative cutoffs, and reasons for testing, were reviewed. Results.--Participant growth was steady for qualitative COT testing. Participation was stable for NIC, ANAB, and quantitative COT testing. Overall, participants performed well on survey challenges. However, reporting thresholds were widely divergent, ranging from 10 to 3000 ng/mL and 0.5 to 300 ng/mL, respectively, for qualitative and quantitative COT testing. Screening cutoffs were as high as 100 ng/mL for ANAB and 1000 ng/mL for NIC. Conclusions.--Although participating laboratories performed well on the NTA Survey, the wide diversity of qualitative and quantitative reporting thresholds creates substantial risk for misinterpretation of results, and could lead to analytical concerns such as excessively high falsenegative or false-positive rates. NIC-related testing would benefit from evidence-based guidelines to drive standardization of reporting. (Arch Pathol Lab Med. 2023;147:634-642; doi: 10.5858/arpa.2022-0094-CP)

Introduction Neonicotinoid insecticides (NEOs) are now the most widely used neurotoxic insecticides on 140 crops in 120 countries. (1) Global use of NEOs has caused growing concerns for decline of [...]

Untargeted global metabolic profiling by liquid chromatography-mass spectometry generates numerous signals that are due to unknown compounds and whose identification forms an important challenge. The analysis of metabolite fragmentation patterns, following collisioninduced dissociation, provides a valuable tool for identification, but can be severely impeded by close chromatographic coelution of distinct metabolites. We propose a new algorithm for identifying related parent-fragment pairs and for distinguishing these from signals due to unrelated compounds. Unlike existing methods, our approach addresses the problem by means of a hypothesis test that is based on the distribution of the recorded ion counts, and thereby provides a statistically rigorous measure of the uncertainty involved in the classification problem. Because of technological constraints, the test is of primary use at low and intermediate ion counts, above which detector saturation causes substantial bias to the recorded ion count. The validity of the test is demonstrated through its application to pairs of coeluting isotopologues and to known parent-fragment pairs, which results in test statistics consistent with the null distribution. The performance of the test is compared with a commonly used Pearson correlation approach and found to be considerably better (e.g., false positive rate of 6.25%, compared with a value of 50% for the correlation for perfectly coeluting ions). Because the algorithm may be used for the analysis of high-mass compounds in addition to metabolic data, we expect it to facilitate the analysis of fragmentation patterns for a wide range of analytical problems. 10.1021/ac902361f