scholarly journals Accidental intoxications in toddlers: lack of cross-reactivity of vilazodone and its urinary metabolite M17 with drug of abuse screening immunoassays

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Christina D. Martinez-Brokaw ◽  
Joshua B. Radke ◽  
Joshua G. Pierce ◽  
Alexandra Ehlers ◽  
Sean Ekins ◽  
...  
2010 ◽  
Vol 134 (5) ◽  
pp. 735-739 ◽  
Author(s):  
Stacy E. F. Melanson ◽  
Leland Baskin ◽  
Barbarajean Magnani ◽  
Tai C. Kwong ◽  
Annabel Dizon ◽  
...  

Abstract Context.—To assist with patient diagnosis and management, physicians from pain services, drug treatment programs, and the emergency department frequently request that urine be tested for drugs of abuse. However, urine immunoassays for drugs of abuse have limitations. Objective.—To use data from the College of American Pathologists Proficiency Testing Surveys to determine and summarize the characteristics, performance, and limitations of urine immunoassays for drugs of abuse. Design.—Six years of urine drug testing proficiency surveys were reviewed. Results.—Lysergic acid diethylamide and methaqualone are infrequently prescribed or abused and, therefore, testing may be unnecessary. However, implementation of more specific testing for methylenedioxymethamphetamine and oxycodone may be warranted. Each drug of abuse immunoassay exhibits a different cross-reactivity profile. Depending on the cross-reactivity profile, patients with clinically insignificant concentrations of drugs may have false-positive results, and patients with clinically significant concentrations of drugs may have false-negative results. Conclusions.—Laboratory directors should be aware of the characteristics of their laboratories' assays and should communicate these characteristics to physicians so that qualitative results can be interpreted more accurately. Furthermore, manufacturer's claims should be interpreted with caution and should be verified in each organization's patient population, if possible.


2009 ◽  
Vol 55 (6) ◽  
pp. 1203-1213 ◽  
Author(s):  
Matthew D Krasowski ◽  
Mohamed G Siam ◽  
Manisha Iyer ◽  
Anthony F Pizon ◽  
Spiros Giannoutsos ◽  
...  

Abstract Background: Immunoassays used for routine drug of abuse (DOA) and toxicology screening may be limited by cross-reacting compounds able to bind to the antibodies in a manner similar to the target molecule(s). To date, there has been little systematic investigation using computational tools to predict cross-reactive compounds. Methods: Commonly used molecular similarity methods enabled calculation of structural similarity for a wide range of compounds (prescription and over-the-counter medications, illicit drugs, and clinically significant metabolites) to the target molecules of DOA/toxicology screening assays. We used various molecular descriptors (MDL public keys, functional class fingerprints, and pharmacophore fingerprints) and the Tanimoto similarity coefficient. These data were then compared with cross-reactivity data in the package inserts of immunoassays marketed for in vitro diagnostic use. Previously untested compounds that were predicted to have a high probability of cross-reactivity were tested. Results: Molecular similarity calculated using MDL public keys and the Tanimoto similarity coefficient showed a strong and statistically significant separation between cross-reactive and non–cross-reactive compounds. This result was validated experimentally by discovery of additional cross-reactive compounds based on computational predictions. Conclusions: The computational methods employed are amenable toward rapid screening of databases of drugs, metabolites, and endogenous molecules and may be useful for identifying cross-reactive molecules that would be otherwise unsuspected. These methods may also have value in focusing cross-reactivity testing on compounds with high similarity to the target molecule(s) and limiting testing of compounds with low similarity and very low probability of cross-reacting with the assay.


1977 ◽  
Vol 23 (5) ◽  
pp. 873-876 ◽  
Author(s):  
C T Viswanathan ◽  
H E Booker ◽  
P G Welling

Abstract A radioimmunoassay for barbiturates is shown to be equally sensitive to phenobarbital and its major urinary metabolite, p-hydroxyphenobarbital, in serum and urine. Interference by the metabolite can be essentially eliminated by selectively extracting phenobarbital into chloroform. The extraction efficiency of the method for phenobarbital was 93+/-2% (SD) over the concentration range studied. Although cross reactivity between barbiturates and their metabolites may be less important in determining cases of barbiturates abuse or overdose, it may be extremely important if data on serum or urine are required for accurate estimates of drug disposition, or in establishing dose/response relationships.


2010 ◽  
Vol 44 (4) ◽  
pp. 1-8
Author(s):  
ALICIA AULT
Keyword(s):  

JAMA ◽  
1966 ◽  
Vol 196 (12) ◽  
pp. 1089-1091 ◽  
Author(s):  
J. L. Claghorn
Keyword(s):  

1979 ◽  
Author(s):  
Daniel Walz ◽  
Thomas Brown

Human prothrombin activation is unique in that, in addition to the release of fragment 1.2 (FI.2) from the NH-terminus of prothrombin by factor Xa during the generation of thrombin, an additional 13 residue polypeptide, fragment 3 (F3), is autocatalytically removed from the amino-terminus of the thrombin A chain. We have developed a rapid radioimmunoassay for human F3 which incorporates short incubation times and the use of a preprecipitated second antibody; the assay can be performed in three hours. Specificity studies in buffer systems show prothrombin and prethrombin 1 cross-reacting at a level of 0.001; purified thrombin does not cross-react. In the presence of 5% BSA, prothrombin displays considerably less cross-reactivity. No immunoreactive material to F3 antibodies could be detected in 400 μL of plasma. Serum, obtained from whole blood clotting, contained measurable quantities of F3 (40-100 ng/mL). This amount in serum represents only 5-10% of the theoretical amount available should all of the fragment be hydrolytically cleaved during the conversion of prothrombin to thrombin. This assay procedure is currently being utilized to monitor the activation of purified human prothrombin in the absence and presence of selected plasma inhibitors. (Supported in part by NIH 05384-17 and the Michigan Heart Association).


1961 ◽  
Vol 38 (3) ◽  
pp. 469-472 ◽  
Author(s):  
K. R. Laumas ◽  
J. F. Tait ◽  
S. A. S. Tait

ABSTRACT Reconsideration of the question of the validity of the calculations of the secretion rates from the specificity activity of a urinary metabolite after the single injection of a radioactive hormone has led us to conclude that the basic equations used in a previous theoretical treatment are not generally applicable to the nonisotopic steady state if the radioactive steroid and hormone are introduced into the same compartment. If this is so, in a two compartmental model with metabolism occurring in both pools, it is now shown that the calculation (S = R — τ) is rigorously valid if certain precautions are taken. This is in contrast to the previous treatment which concluded (in certain special circumstances) that the calculation might not be correct. However, if the hormone is secreted in both compartments and the radioactive steroid is injected into only one, then the calculation (S = R — τ) may not be correct in certain circumstances as was previously concluded (Laumas et al. 1961).


Diabetes ◽  
1987 ◽  
Vol 36 (11) ◽  
pp. 1268-1270
Author(s):  
K. Kover ◽  
O. Hegre ◽  
H. Popiela ◽  
T. Biggs ◽  
W. V. Moore

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