A Case of False-positive Amphetamine Results on Urine Toxicology Testing Secondary to Imatinib

Meyers, Sarah; Wachman, Elisha M.

doi:10.1097/adm.0000000000000766

Cited by 4 publications

(1 citation statement)

References 10 publications

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“…In drugs‐of‐abuse studies and applied toxicology testing, initial identification of drugs and their metabolites in biological fluids is most often performed by immunoassay methods that provide only qualitative and presumptive evidence of drug classes. Although studies have shown a significant incidence of both false positives and false negatives by presumptive immunoassay screening techniques, more sensitive and selective methods of definitive drug identification by LC‐ESI‐MS/MS continue to be reserved for use in more limited confirmation and quantitation testing (Darragh, Snyder, Ptolemy, & Melanson, 2014; Macher & Penders, 2012; Manchikanti, Malla, Wargo, & Fellows, 2011; Meyers & Wachman 2010; Mikel, Pesce, Rosenthal, & West, 2012; Pesce et al., 2010; Saitman, Park, & Fitzgerald, 2014; West et al., 2010). With more recent advances in automated drug testing by LC‐MS technology, it is instrumentally possible to employ direct‐to‐definitive methods of high‐volume drug testing in both basic and applied toxicology studies.…”

Section: Commentarymentioning

confidence: 99%

Novel Matrix Normalization Technique for Accurate LC‐ESI‐MS/MS Detection and Quantification of Drugs and Their Metabolites in Toxicology Research and Practice

Rosano

Rumberger²,

Scholz³

et al. 2023

Current Protocols

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Accurate identification and quantification of drugs and their metabolites (analytes) in biological matrices is an analytical foundation of clinical and forensic toxicology. For decades, liquid chromatography interfaced by electrospray ionization with tandem mass spectrometry (LC‐ESI‐MS/MS) has been a widely used technology for analysis in the field of toxicology, as well as in many other fields of bioscience. It is also known that ion response in LC‐ESI‐MS/MS analysis is influenced by coeluting biological compounds and that preanalytical sample clean‐up is often insufficient in removing these interferences. As a result, a normalization technique is commonly used for assessment and compensation of matrix effects encountered in routine analysis. Internal standardization with a stable isotope analog of the analyte is the predominant normalization technique used in LC‐ESI‐MS/MS analysis. The technique, however, requires commercial availability or costly custom synthesis of an isotopic analog specific for each analyte. Here we describe an alternative technique for matrix normalization for use in high‐volume, multianalyte testing without the need for isotope analogs. The technique involves analysis of the original sample (neat analysis) followed by analysis of a second sample aliquot (spike analysis) that has been fortified with a controlled amount of reference analyte. A calibration procedure similar to internal standardization is employed, using an ion response ratio of neat to fortified analyte. As a demonstration of the technique in multianalyte testing, we provide a detailed protocol for simultaneous detection and quantification of 102 drugs and drug metabolites in human urine. We also provide a support protocol for addition of new analytes to the multianalyte panel, allowing convenient collection of the validation data during routine testing. The matrix normalization technique and testing principles may be applicable to a wide range of analytes and biological matrices, not only those encountered in toxicology but also in other fields of bioscience. © 2023 Wiley Periodicals LLC. Basic Protocol: Detection and quantification of 102 toxicology analytes in urine by LC‐ESI‐MS/MS analysis using the threshold accurate calibration technique Support Protocol: Method for addition and validation of new analytes to expand the Basic Protocol

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Section: Commentarymentioning

confidence: 99%

Novel Matrix Normalization Technique for Accurate LC‐ESI‐MS/MS Detection and Quantification of Drugs and Their Metabolites in Toxicology Research and Practice

Rosano

Rumberger²,

Scholz³

et al. 2023

Current Protocols

View full text Add to dashboard Cite

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Reconsidering the use of urine drug testing in reproductive settings

Martinez,

Roberts,

Achu-Lopes

et al. 2023

American Journal of Obstetrics & Gynecology MFM

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False-Positive Amphetamines in Urine Drug Screens: A 6-Year Review

Pope

Drummer

Schneider

2022

Journal of Analytical Toxicology

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Immunoassays are routinely used to provide rapid urine drug screening results in the clinical setting. These screening tests are prone to false positive results and ideally require confirmation by mass spectrometry. In this study, we have examined a large number of urine specimens where drugs other than the amphetamines may have caused a false positive amphetamine immunoassay screening result. 12,250 urine drug screens in a clinical laboratory that used the CEDIA amphetamine/ecstasy method were reviewed for false positive results over a six-year period (2015-2020). An additional 3,486 referred samples, where confirmatory mass spectrometry was requested were also reviewed. 86 in-house samples and 175 referral samples that were CEDIA false positives screens were further analyzed by an LC–QTOF general unknown screen. Potential cross-reacting drugs were identified and their molecular similarities to the CEDIA targets were determined. Commercial standards were also analyzed for cross-reactivity in the amphetamine/ecstasy CEDIA screen. Positive amphetamine results in 3.9% of in-house samples and 9.9% of referred tests for confirmatory analysis were false positive for amphetamines. Of these false positive specimens, on average, 6.8 drugs were detected by the LC–QTOF screen. Several drugs were identified as possible cross-reacting drugs to the CEDIA amphetamine/ecstasy assay. Maximum common substructure scores for 70 potential cross-reacting compounds were calculated. This was not helpful in identifying cross reacting drugs. False positive amphetamine screens make up to 3.9 – 9.9% of positive amphetamine screens in the clinical laboratory. Knowledge of cross-reacting drugs may be helpful when mass spectrometry testing is unavailable.

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A Case of False-positive Amphetamine Results on Urine Toxicology Testing Secondary to Imatinib

Cited by 4 publications

References 10 publications

Novel Matrix Normalization Technique for Accurate LC‐ESI‐MS/MS Detection and Quantification of Drugs and Their Metabolites in Toxicology Research and Practice

Novel Matrix Normalization Technique for Accurate LC‐ESI‐MS/MS Detection and Quantification of Drugs and Their Metabolites in Toxicology Research and Practice

Reconsidering the use of urine drug testing in reproductive settings

False-Positive Amphetamines in Urine Drug Screens: A 6-Year Review

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