Effect of the traditional chinese medicines Chan Su, Lu‐Shen‐Wan, Dan Shen, and Asian Ginseng on Serum Digoxin measurement by Tina‐quant (Roche) and Synchron LX system (Beckman) digoxin immunoassays

Abstract

Chan Su, Lu-Shen-Wan, Dan Shen, and Asian ginseng are traditionally used to treat a number of conditions, including cardiovascular disease. All of these traditional Chinese medicines exhibit cardioactive properties. Digoxin is a cardioactive drug with a narrow therapeutic range (0.8-1.9 ng/mL). A patient taking digoxin may also take these Chinese medicines for their cardiotonic effects. Moreover, the active components of these medicines that are responsible for cardiotonic effects bear structural similarities to digoxin. Therefore, we studied the potential interference of these Chinese medicines with two digoxin immunoassays--the Tina-quant (Roche Diagnostics) and the Beckman (Synchron LX system)--and compared the values with the fluorescence polarization immunoassay (FPIA; Abbott Laboratories). When very small amounts (2-5 microL) of aqueous extract of Chan Su or Lu-Shen-Wan were added to drug-free serum, we observed high digoxin-like immunoreactivity with the FPIA. In contrast, when ethyl acetate extract of Dan Shen or microliter amounts of ginseng extract were added to drug-free serum, we observed modest digoxin-like immunoreactivity with the FPIA, but no apparent digoxin activity with the Roche and Beckman digoxin immunoassays. When aliquots of a digoxin pool prepared from patients receiving digoxin were supplemented with these Chinese medicines, we observed the most significant interference with the FPIA. The presence of endogenous digoxin-like immunoreactive substances can have additive effects with these Chinese medicines and falsely increase apparent digoxin levels by the FPIA. On the other hand, the Roche and Beckman assays were free from interference from DLIS but showed significant interference from Chan Su and Lu-Shen-Wan. We conclude that the FPIA showed the most significant interference from all four of the Chinese medicines we studied. However, the Roche and Beckman assays showed no interference from two (Dan Shen and Asian ginseng) of the four Chinese medicines we studied.

Cardiovascular effects of Danshen

“…Taking advantage of poor protein binding of digoxin (25%) and high protein binding of digoxin-like immunoreactive components of Danshen, Wahed and Dasgupta [120] and Dasgupta [121] demonstrated that the positive and negative interferences of Danshen in serum digoxin measurement can be eliminated by monitoring the free digoxin concentration. On the other hand, the EMIT 2000 (Dade Behring, Deerpark, IL) [122], Randox (Randox Labs Ltd., Antrim, UK) [122], CLIA (Bayer Diagnostics, Tarrytown, NY) [122], Tina-quant (Roche Diagnostics) [123] and Synchron LX system (Beckman) [123] immunoassays for digoxin showed no interference from Danshen.…”

Validation and application of a 96-well format solid-phase extraction and liquid chromatography–tandem mass spectrometry method for the quantitation of digoxin in human plasma

“…However, the lower limit of quantitation of immunoassays which are commonly used method for digoxin assays (0.1-0.4 ng/mL, see Table 1) are not sensitive enough to evaluate the pharmacokinetics of digoxin administered at less than 0.25 mg such as 0.125 mg. It has been reported that immunoassays are relatively nonspecific and cross-react with digoxin metabolites and endogenous digoxin-like substances [11][12][13][14][15][16]. Recently, LC/MS/MS, which is highly sensitive and specific, has become accepted as the leading technique for the quantitation of exogenous substances in biological samples.…”

Rapid separation and determination of resibufogenin and cinobufagin in toad venom and Liushen tablet by β-cyclodextrin modified micellar electrokinetic chromatography

“…These Chinese medications have been widely used in China, Japan and other Asian countries for a long time, and over the last decade, have gained considerable favor in the United States and other places of the world. Toad venom is used as a topical anesthetic and cardiac medication [3,4]. It can eliminate toxic material; relieve carbuncle, furuncle, cellulites and multiple abscesses [5].…”