LC-MS/MS Techniques for High-Volume Screening of Drugs of Abuse and Target Drug Quantitation in Urine/Blood Matrices

Author(s):  
Jeff C. Eichhorst ◽  
Michele L. Etter ◽  
Patricia L. Hall ◽  
Denis C. Lehotay
2020 ◽  
Author(s):  
Nadia Ayala-Lopez ◽  
Layla Aref ◽  
Jennifer M. Colby ◽  
Jacob J. Hughey

AbstractBackgroundUrine drug screening (UDS) assays can rapidly and sensitively detect drugs of abuse, but can also produce spurious results due to interfering substances. We previously developed an approach to identify interfering medications using electronic health record (EHR) data, but the approach was limited to UDS assays for which presumptive positives were confirmed using more specific methods. Here we adapted the approach to search for medications that cause false positives on UDS assays lacking confirmation data.MethodsFrom our institution’s EHR data, we used our previous dataset of 698,651 UDS and confirmation results. We also collected 211,108 UDS results for acetaminophen, ethanol, and salicylates. Both datasets included individuals’ prior medication exposures. We hypothesized that the odds of a presumptive positive would increase following exposure to an interfering ingredient independently of exposure to the assay’s target drug(s). For a given assay-ingredient pair, we quantified potential interference as an odds ratio from logistic regression. We evaluated interference of selected compounds in spiking experiments.ResultsCompared to the approach requiring confirmation data, our adapted approach showed only modestly diminished ability to detect interfering ingredients. Applying our approach to the new data, three ingredients had a higher odds ratio on the acetaminophen assay than acetaminophen itself did: levodopa, carbidopa, and entacapone. The first two, as well as related compounds methyldopa and alpha-methyldopamine, produced presumptive positives at < 40 μg/mL.ConclusionsOur approach can reveal interfering medications using EHR data from institutions at which UDS results are not routinely confirmed.


Author(s):  
Nadia Ayala-Lopez ◽  
Layla Aref ◽  
Jennifer M Colby ◽  
Jacob J Hughey

Abstract Urine drug screening (UDS) assays can rapidly and sensitively detect drugs of abuse but can also produce spurious results due to interfering substances. We previously developed an approach to identify interfering medications using electronic health record (EHR) data, but the approach was limited to UDS assays for which presumptive positives were confirmed using more specific methods. Here we adapted the approach to search for medications that cause false positives on UDS assays lacking confirmation data. From our institution’s EHR data, we used our previous dataset of 698,651 UDS and confirmation results. We also collected 211,108 UDS results for acetaminophen, ethanol and salicylates. Both datasets included individuals’ prior medication exposures. We hypothesized that the odds of a presumptive positive would increase following exposure to an interfering medication independently of exposure to the assay’s target drug(s). For a given assay–medication pair, we quantified potential interference as an odds ratio from logistic regression. We evaluated interference of selected compounds in spiking experiments. Compared to the approach requiring confirmation data, our adapted approach showed only modestly diminished ability to detect interfering medications. Applying our approach to the new data, we discovered and validated multiple compounds that can cause presumptive positives on the UDS assay for acetaminophen. Our approach can reveal interfering medications using EHR data from institutions at which UDS results are not routinely confirmed.


1993 ◽  
Vol 39 (10) ◽  
pp. 2137-2146 ◽  
Author(s):  
D A Armbruster ◽  
R H Schwarzhoff ◽  
E C Hubster ◽  
M K Liserio

Abstract The newest formulation of the Syva EMIT assay for drugs of abuse, EMIT II, and a new immunoassay, OnLine (Roche), utilizing the kinetic interaction of microparticles in solution (KIMS) methodology, RIA tests, and TDx fluorescence polarization immunoassay (FPIA) procedures were compared for marijuana, cocaine, opiates, and barbiturates. Both EMIT II and OnLine immunoassays were performed with a Hitachi 717 analyzer. Calibration curves, the degree of separation between negative and cutoff calibrators, precision, likelihood of carryover from positive to negative samples, and overall ease and speed of analysis were evaluated. RIA and OnLine detected 99% of gas chromatography/mass spectrometry (GC/MS)-confirmed marijuana samples; TDx, 95%; and EMIT II, 88%. All four immunoassays detected approximately 99% of confirmed cocaine-positive urines. RIA, OnLine, and TDx all detected 100% of opiate-confirmed samples; EMIT II, 97%. Barbiturate assays exhibited the greatest disparity, with OnLine and TDx detecting 100% of confirmed positives; EMIT II, 88%; and RIA, 78%. For a variety of reasons, we prefer the fully automated EMIT II and OnLine assays for high-volume urine testing, in comparison with our laboratory's semiautomated RIA tests and the limited-throughput TDx system. The four immunoassays investigated delivered comparable performance in terms of detection rates for GC/MS-confirmed positives for some drugs but not for others.


Author(s):  
D. E. Fornwalt ◽  
A. R. Geary ◽  
B. H. Kear

A systematic study has been made of the effects of various heat treatments on the microstructures of several experimental high volume fraction γ’ precipitation hardened nickel-base alloys, after doping with ∼2 w/o Hf so as to improve the stress rupture life and ductility. The most significant microstructural chan§e brought about by prolonged aging at temperatures in the range 1600°-1900°F was the decoration of grain boundaries with precipitate particles.Precipitation along the grain boundaries was first detected by optical microscopy, but it was necessary to use the scanning electron microscope to reveal the details of the precipitate morphology. Figure 1(a) shows the grain boundary precipitates in relief, after partial dissolution of the surrounding γ + γ’ matrix.


Author(s):  
M.G. Burke ◽  
M.K. Miller

Interpretation of fine-scale microstructures containing high volume fractions of second phase is complex. In particular, microstructures developed through decomposition within low temperature miscibility gaps may be extremely fine. This paper compares the morphological interpretations of such complex microstructures by the high-resolution techniques of TEM and atom probe field-ion microscopy (APFIM).The Fe-25 at% Be alloy selected for this study was aged within the low temperature miscibility gap to form a <100> aligned two-phase microstructure. This triaxially modulated microstructure is composed of an Fe-rich ferrite phase and a B2-ordered Be-enriched phase. The microstructural characterization through conventional bright-field TEM is inadequate because of the many contributions to image contrast. The ordering reaction which accompanies spinodal decomposition in this alloy permits simplification of the image by the use of the centered dark field technique to image just one phase. A CDF image formed with a B2 superlattice reflection is shown in fig. 1. In this CDF micrograph, the the B2-ordered Be-enriched phase appears as bright regions in the darkly-imaging ferrite. By examining the specimen in a [001] orientation, the <100> nature of the modulations is evident.


2020 ◽  
Vol 47 (6) ◽  
pp. 789-792
Author(s):  
François R. Sylvestre ◽  
Beatriz P. Monteiro ◽  
Marie-Josée Simard ◽  
Paulo V. Steagall

2007 ◽  
Vol 177 (4S) ◽  
pp. 331-331 ◽  
Author(s):  
Stephen D.W. Beck ◽  
Richard S. Foster ◽  
Richard Bihrle ◽  
John P. Donohue

2006 ◽  
Vol 175 (4S) ◽  
pp. 8-9 ◽  
Author(s):  
Brent K. Hollenbeck ◽  
Yongliang Wei ◽  
John D. Birkmeyer

VASA ◽  
2019 ◽  
Vol 48 (6) ◽  
pp. 516-522 ◽  
Author(s):  
Verena Mayr ◽  
Mirko Hirschl ◽  
Peter Klein-Weigel ◽  
Luka Girardi ◽  
Michael Kundi

Summary. Background: For diagnosis of peripheral arterial occlusive disease (PAD), a Doppler-based ankle-brachial-index (dABI) is recommended as the first non-invasive measurement. Due to limitations of dABI, oscillometry might be used as an alternative. The aim of our study was to investigate whether a semi-automatic, four-point oscillometric device provides comparable diagnostic accuracy. Furthermore, time requirements and patient preferences were evaluated. Patients and methods: 286 patients were recruited for the study; 140 without and 146 with PAD. The Doppler-based (dABI) and oscillometric (oABI and pulse wave index – PWI) measurements were performed on the same day in a randomized cross-over design. Specificity and sensitivity against verified PAD diagnosis were computed and compared by McNemar tests. ROC analyses were performed and areas under the curve were compared by non-parametric methods. Results: oABI had significantly lower sensitivity (65.8%, 95% CI: 59.2%–71.9%) compared to dABI (87.3%, CI: 81.9–91.3%) but significantly higher specificity (79.7%, 74.7–83.9% vs. 67.0%, 61.3–72.2%). PWI had a comparable sensitivity to dABI. The combination of oABI and PWI had the highest sensitivity (88.8%, 85.7–91.4%). ROC analysis revealed that PWI had the largest area under the curve, but no significant differences between oABI and dABI were observed. Time requirement for oABI was significantly shorter by about 5 min and significantly more patients would prefer oABI for future testing. Conclusions: Semi-automatic oABI measurements using the AngER-device provide comparable diagnostic results to the conventional Doppler method while PWI performed best. The time saved by oscillometry could be important, especially in high volume centers and epidemiologic studies.


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