Aliquots Of Drug-free Serum Pool Research Articles

Effect of Chinese Medicine Danshen and Indian Ayurvedic Medicine Bark of Arjuna Tree on a Relatively New LOCI Digoxin Assay for Application on the Vista 1500 Analyzer.

Danshen is a traditional Chinese medicine and bark of Arjuna tree is an Ayurvedic medicine both indicated as heart tonic. Interference of Danshen in serum digoxin immunoassays has been reported but potential interference of extract of bark of Arjuna tree has not been reported. We studied potential interferences of Danshen and bark of Arjuna tree on a relatively new LOCI digoxin assay for application on the Vista 1500 analyzer (Siemens Diagnostics). Aliquots of drug-free serum were supplemented with ethyl acetate extract of Danshen (two different brands studied) or aqueous or ethyl alcohol extract of bark of Arjuna tree and apparent digoxin concentrations were measured by the LOCI digoxin assay. In another experiment, aliquots of serum pool containing digoxin were further supplemented with Danshen or bark of Arjuna tree extract and digoxin concentrations were measured again using LOCI digoxin assay. Little apparent digoxin concentration was observed when aliquots of drug-free serum pools were supplemented with Danshen or bark of Arjuna tree extract. When aliquots of serum digoxin pool were further supplemented with these extract, we observed statistically significant negative interference but such differences may not be clinically significant. We conclude that LOCI digoxin assay is virtually free from interferences of Danshen and extract of bark of Arjuna tree.

Digoxin Immunoassays on the ARCHITECT i2000SR and ARCHITECT c8000 Analyzers Are Free From Interferences of Asian, Siberian, and American Ginseng

Asian, Siberian, and American ginseng are known to interfere with serum digoxin measurements using fluorescence polarization technology, Digoxin II and Digoxin III assays (Abbott Laboratories, Green oaks, IL) as well as other digoxin assays. Abbott Laboratories more recently launched two new digoxin assays: iDigoxin, a chemiluminescent microparticle immunoassay for application on the ARCHITECT i1000SR and i2000SR immunoassay analyzers, and cDigoxin, a particle-enhanced turbidimetric inhibition immunoassay for application on the ARCHITECT c4000, c8000, and c1600 clinical chemistry analyzers; and we studied potential interferences of ginsengs with these two assays in vitro. When aliquots of drug-free serum pool treated with activated charcoal were supplemented with extracts of various ginsengs, no significant apparent digoxin values were observed. In addition, when aliquots of the digoxin pool prepared from patients taking digoxin were further supplemented with these ginseng extracts and the digoxin values were re-measured, we observed no statistically significant difference in observed digoxin values compared to the original digoxin value of the pool. These results further establish that relatively new digoxin assays for application on the ARCHITECT analyzers that employ specific monoclonal antibodies against digoxin are free from interferences from Asian, Siberian, and American ginseng.

Abbott ARCHITECT Clinical Chemistry and Immunoassay Systems: Digoxin Assays Are Free of Interferences From Spironolactone, Potassium Canrenoate, and Their Common Metabolite Canrenone

Spironolactone, which is metabolized to canrenone, is often used in combination with digoxin. Potassium canrenoate is a similar drug that is also metabolized to canrenone. As a result of reported interference of spironolactone, potassium canrenoate, and their common metabolite canrenone with digoxin immunoassays, we investigated potential interference of these compounds with two relatively new digoxin assays for application on ARCHITECT clinical chemistry platforms (cDig, particle-enhanced turbidimetric inhibition immunoassay) and ARCHITECT immunoassay platforms (iDig, chemiluminescent microparticle immunoassay), both from Abbott Diagnostics. When aliquots of drug-free serum pool were supplemented with various amounts of spironolactone, potassium canrenoate, and canrenone, no apparent digoxin concentration was observed using cDig assay on ARCHITECT c4000, c8000, and c16000 or iDig assay on i1000SR and i2000SR analyzers. In addition, we observed no false increase in serum digoxin value when aliquots of a digoxin pool were further supplemented with various amounts of spironolactone, potassium canrenoate, or canrenone. We conclude that both the cDig and iDig assays on the ARCHITECT analyzers are free from interferences by spironolactone, potassium canrenoate, and canrenone.

Rapid detection of oleander poisoning by Dimension Vista digoxin assay (Flex Reagent Cartridge)

Oleander poisoning can be detected by digoxin immunoassays and for last two decades the fluorescence polarization immunoassay (FPIA) has been used for rapid detection of oleander poisoning in clinical laboratories. Recently, Abbott Laboratories (Abbott Park, IL) discontinued this assay. Therefore, we explored the possibility of using another digoxin assay (Dimension Vista Flex Reagent Cartridge, Tina Quant, EMIT 2000 and old FPIA assay for comparison) for rapid detection of oleander poisoning. When aliquots of drug-free serum pools were supplemented with pure oleandrin or oleander extract, we observed the highest apparent digoxin values using Dimension Vista digoxin assay (Flex Reagent Cartridge). We also observed significant apparent digoxin values in vivo in sera of mice both 1 and 2 hr after feeding with oleander extract. When a serum pool prepared from patients taking digoxin was further supplemented with various amounts of oleander extract, the highest falsely elevated digoxin values were observed with Dimension Vista digoxin assay. Monitoring free digoxin using Dimension Vista digoxin assay (Flex Reagent Cartridge) did not eliminate this interference. Digibind neutralized digoxin-like factors of oleander extract and such effect can be monitored by observing significant reduction in apparent free digoxin levels in the presence of Digibind as measured in the protein-free ultrafiltrate using Dimension Vista digoxin assay (Flex Reagent Cartridge).

Rapid Detection of Oleander Poisoning by Digoxin III, a New Digoxin Assay

We studied the potential for detecting oleander with a new immunoassay (Digoxin III, Abbott Laboratories, Abbott Park, IL) by comparing results with those from the fluorescence polarization immunoassay (FPIA) and Digoxin II assay (Abbott). In aliquots of drug-free serum pools supplemented with pure oleandrin or oleander extract, we observed apparent digoxin values using all 3 immunoassays, but values obtained by the Digoxin III were higher than obtained by the other assays. We also observed significant apparent digoxin values in vivo in serum samples of mice 1 and 2 hours after feeding oleander extract. The average half-life of digoxin-like factors was 1.1 hours. In a serum pool (prepared from patients taking digoxin) supplemented with oleander extract, the observed digoxin values were falsely lowered when measured by the Digoxin II but falsely elevated when measured by the Digoxin III and FPIA. Monitoring free digoxin using the Digoxin III cannot eliminate this interference. Digibind neutralized digoxin-like factors of oleander extract; the effect can be monitored by observing a significant reduction in apparent free digoxin levels in the presence of Digibind as measured in protein-free ultrafiltrate using the Digoxin III. The Digoxin III is highly sensitive for measuring oleander.

Effect of Asian ginseng, Siberian ginseng, and Indian ayurvedic medicine Ashwagandha on serum digoxin measurement by digoxin III, a new digoxin immunoassay

Asian ginseng, Siberian ginseng, and Indian Ayurvedic medicine Ashwagandha demonstrated modest interference with serum digoxin measurements by the fluorescent polarization immunoassay (FPIA). Recently, Abbott Laboratories marketed a new digoxin immunoassay, Digoxin III for application on the AxSYM analyzer. We studied potential interference of these herbal supplements on serum digoxin measurement by Digoxin III assay in vitro and compared our results with the values obtained by Tina-quant assay. Aliquots of drug-free serum pool were supplemented with various amounts of Asian ginseng, Siberian ginseng, or Ashwagandha approximating expected concentrations after recommended doses and overdoses of these herbal supplements in serum. Then digoxin concentrations were measured by the Digoxin III and Tina-quant (Roche Diagnostics) assay. We also supplemented aliquots of a digoxin pool prepared from patients receiving digoxin with various amounts of these herbal supplements and then measured digoxin concentrations again using both digoxin immunoassays. We observed modest apparent digoxin concentrations when aliquots of drug-free serum pool were supplemented with all three herbal supplements using Digoxin III assay (apparent digoxin in the range of 0.31-0.57 ng/ml), but no apparent digoxin concentration (except with the highest concentration of Ashwagandha supplement for both brands) was observed using the Tina-quant assay. When aliquots of digoxin pool were further supplemented with these herbal supplements, digoxin concentrations were falsely elevated when measured by the new Digoxin III assay. For example, we observed 48.2% (1.63 ng/ml digoxin) increase in digoxin concentration when an aliquot of Digoxin pool 1 (1.10 ng/ml digoxin) was supplemented with 50 microl of Asian ginseng extract (Brand 2). Measuring free digoxin does not eliminate the modest interferences of these herbal supplements in serum digoxin measurement by the Digoxin III assay.

Interference of Asian, American, and Indian (Ashwagandha) ginsengs in serum digoxin measurements by a fluorescence polarization immunoassay can be minimized by using a new enzyme-linked chemiluminescent immunosorbent or turbidimetric assay.

Abstract Context.—Ginsengs are widely used by the general population. These herbs interfere with serum digoxin measurement using the fluorescence polarization immunoassay. Objective.—To assess potential interference of different ginsengs (Asian, American, and Indian, also known as Ashwagandha) in vitro and in vivo in a mouse model by using a new enzyme-linked chemiluminescent immunosorbent digoxin assay and an existing turbidimetric assay. Comparisons were made with the fluorescence polarization immunoassay. Design.—Aliquots of drug-free serum pools were supplemented with ginseng and apparent digoxin concentrations were measured using enzyme-linked chemiluminescent immunosorbent digoxin assay, turbidimetric assay, and fluorescence polarization immunoassay digoxin assays. Mice were fed with different ginseng preparations and apparent digoxin concentrations were measured 1 and 3 hours later. In a separate experiment, aliquots of serum digoxin pools were further supplemented with ginsengs and the serum digox...

Interference of Asian, American, and Indian (Ashwagandha) Ginsengs in Serum Digoxin Measurements by a Fluorescence Polarization Immunoassay Can Be Minimized by Using a New Enzyme-Linked Chemiluminescent Immunosorbent or Turbidimetric Assay

Ginsengs are widely used by the general population. These herbs interfere with serum digoxin measurement using the fluorescence polarization immunoassay. To assess potential interference of different ginsengs (Asian, American, and Indian, also known as Ashwagandha) in vitro and in vivo in a mouse model by using a new enzyme-linked chemiluminescent immunosorbent digoxin assay and an existing turbidimetric assay. Comparisons were made with the fluorescence polarization immunoassay. Aliquots of drug-free serum pools were supplemented with ginseng and apparent digoxin concentrations were measured using enzyme-linked chemiluminescent immunosorbent digoxin assay, turbidimetric assay, and fluorescence polarization immunoassay digoxin assays. Mice were fed with different ginseng preparations and apparent digoxin concentrations were measured 1 and 3 hours later. In a separate experiment, aliquots of serum digoxin pools were further supplemented with ginsengs and the serum digoxin concentrations were measured again. A significant apparent digoxin concentration was observed both in vitro and in vivo using the fluorescence polarization immunoassay, but no apparent digoxin concentration was observed using enzyme-linked chemiluminescent immunosorbent digoxin assay and turbidimetric assay. No interference was observed with enzyme-linked chemiluminescent immunosorbent digoxin assay and turbidimetric assay when digoxin serum pools were further supplemented with various ginsengs. It was concluded that both enzyme-linked chemiluminescent immunosorbent and turbidimetric digoxin assays are free from ginseng interferences.

False-positive Serum Tricyclic Antidepressant Concentrations Using Fluorescence Polarization Immunoassay Due to the Presence of Hydroxyzine and Cetirizine

A recent report indicates that hydroxyzine and its active metabolite cetirizine interfere with the PENTINA carbamazepine assay. The potential interference of hydroxyzine and cetirizine with the fluorescence polarization immunoassay (FPIA) and CEDIA assay of carbamazepine as well as with the fluorescence polarization immunoassay of tricyclic antidepressants (TCA) was studied. Aliquots of drug-free serum pools were supplemented with various concentrations of hydroxyzine and cetirizine representing therapeutic, mild to moderate toxic as well as very toxic concentrations. Then apparent carbamazepine and TCA concentrations were measured by immunoassays. Although no interference of hydroxyzine and cetirizine was observed with carbamazepine assays (FPIA and CEDIA), significant apparent TCA concentrations were observed when aliquots of drug-free serum were supplemented with hydroxyzine or cetirizine. Mathematical formula was devised to predict hydroxyzine and/or cetirizine concentration in serum based on observed apparent TCA levels. Hydroxyzine and cetirizine also falsely increased total TCA values when aliquots of serum pool prepared from patients receiving TCA were further supplemented with these drugs. In conclusion, hydroxyzine and cetirizine do not interfere with the FPIA and CEDIA carbamazepine assays but interfere with the measurement of total TCA using the FPIA.

Turbidimetric carbamazepine immunoassay on the ADVIA® 1650 and 2400 analyzers is free from interference of antihistamine drugs hydroxyzine and cetirizine

A recent report indicates that hydroxyzine and its active metabolite cetirizine interfere with the particle-enhanced turbidimetric inhibition immunoassay (PENTINA) carbamazepine assay. We studied potential interference of hydroxyzine and cetirizine with the turbidimetric carbamazepine immunoassay on ADVIA 1650 and ADVIA 2400 (Bayer Diagnostics, Tarrytown, NY) analyzers. Aliquots of drug-free serum pools were supplemented with various concentrations of hydroxyzine and cetirizine representing therapeutic, moderate toxic, as well as very toxic concentrations. These samples were assayed by the turbidimetric carbamazepine immunoassay on two analyzers. To study the interference in presence of the analyte, aliquots of a serum pool prepared from patients receiving carbamazepine were further supplemented with various amounts of hydroxyzine and or cetirizine and apparent carbamazepine concentrations were measured again in order to compare with the value of original pool. No apparent carbamazepine concentration was observed when aliquots of drug-free serum were supplemented with hydroxyzine or cetirizine. Moreover, in the carbamazepine pool, the original carbamazepine concentration compared well when aliquots of this serum pool were further supplemented with hydroxyzine or cetirizine. We conclude that the turbidimetric carbamazepine immunoassay is free from interference of hydroxyzine and cetirizine.

New Enzyme-Linked Chemiluminescent Immunosorbent Digoxin Assay Is Free From Interference of Chinese Medicine DanShen

DanShen is a traditional Chinese medicine indicated for cardiovascular diseases. The potential interference of DanShen with serum digoxin measurement was investigated using a new enzyme-linked chemiluminescent immunosorbent (ECLIA) digoxin assay. Aliquots of drug-free serum were supplemented with ethyl acetate extract of DanShen (4 different brands studied), and apparent digoxin concentrations were measured by the ECLIA as well as fluorescence polarization immunoassay (FPIA) and a turbidimetric assay for comparison. Mice were also fed 4 DanShen preparations and apparent digoxin concentrations were subsequently measured. In another experiment, serum pools containing digoxin were further supplemented with DanShen extracts and digoxin concentrations were measured again by all 3 assays. No apparent digoxin concentration was observed when aliquots of drug-free serum pools were supplemented with DanShen and digoxin concentrations were measured by the ECLIA or the turbidimetric assay. In contrast, significant apparent digoxin concentrations were observed using FPIA, and the highest apparent digoxin concentration was observed with brand 4 of DanShen extract. Similarly, when mice were fed with this herb, significant apparent digoxin concentrations were also observed using FPIA, but neither ECLIA nor turbidimetric assay showed any apparent digoxin concentration. When aliquots of digoxin pool were further supplemented with various DanShen extract, the apparent digoxin concentrations were significantly increased when FPIA was used. In contrast, digoxin concentrations in the presence of DanShen extract compared well with the digoxin concentration of the original pool when ECLIA or turbidimetric assay was used. We conclude that DanShen does not interfere with serum digoxin measurement using a more recently released ECLIA digoxin assay.

The New Enzyme-Linked Immunosorbent Digoxin Assay on the ADVIA Integrated Modular System® is Virtually Free From Oleander Interference

Despite known toxicity of oleander, this product is used in herbal preparations. Oleander interferes with various digoxin immunoassays. It is possible that a person taking digoxin also may take oleander-containing herbal products, and digoxin immunoassays interfering with oleander cannot be used for therapeutic monitoring of digoxin. Recently, Bayer Diagnostics introduced a new enzyme-linked chemiluminescent immunosorbent digoxin assay for application on the ADVIA IMS System (ECLIA-digoxin). We studied potential interference of oleander with this new digoxin assay and found that this assay is virtually free from oleander interference. When aliquots of drug-free serum pools were supplemented with ethyl alcohol extract of oleander leaf or pure oleandrin standard, we observed significant apparent digoxin concentration when measured by the fluorescence polarization immunoassay (FPIA) but minimal digoxin-like immunoreactivity using the ECLIA digoxin assay. Because cross-reactivity should be studied in the presence of primary analyte, we prepared 2 serum pools using sera from patients receiving digoxin. Then aliquots of first digoxin pool were supplemented with oleandrin standard and aliquots of second digoxin pool with oleander extract. We observed significant increases in apparent digoxin concentration in the presence of both oleandrin and oleander extract using the FPIA. However, we observed no statistically significant change in digoxin concentration when ECLIA digoxin assay was used, indicating that this assay is virtually free from oleander interference.