Urinary digoxin-like immunoreactive substance in pregnancy

Frıedman, Howard S.; Abramowitz, Ira; Nguyen, T.T.; Babb, Bernardine; Stern, Milton; Farrer, Sanford M.; Tricomi, Vincent

doi:10.1016/0002-9343(87)90695-4

Cited by 9 publications

(2 citation statements)

References 18 publications

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“…The used anti-serum clearly discriminated Dg from its metabolites, 3) so the observed discrepancy could come from DLIS. DLIS has been reported in the sera of pregnant women, 10) newborn infants, 11) patients with renal 12) or hepatic disease. 13) The further experiments considering the patients' background are necessary to recognize the effect of DLIS with immunoassay, which can clarify the scope and limitation of immunoassay for the determination of Dg or digitoxin concentration in human fluids.…”

Section: Determination Of Dg In Sera Obtained From Digitalizedmentioning

confidence: 99%

Determination of Digoxin in Human Serum Using Stable Isotope Dilution Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry

Mitamura

Horikawa

Yamane

et al. 2007

Biological & Pharmaceutical Bulletin

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Digitalis glycosides, represented by digoxin (Dg) and digitoxin, have been commonly used for the treatment of congestive heart failure and other cardiac diseases. In addition to the narrow therapeutic range of the serum digitalis glycosides, their bioavailability is easily affected by kidney or liver failure and the dosing of other medicines. Therefore, it is important to accurately measure the digitalis glycosides in sera from digitalized patients.Dg has been more commonly used than digitoxin and its therapeutic range in serum is 0.8-2.0 ng/ml. 1) Immunoassay is routinely used for therapeutic drug monitoring (TDM) of Dg. However, the commercially available antibodies show a high cross-reactivity with Dg metabolites, such as digoxigenin bisdigitoxoside (Bis-Dggenin), digoxigenin monodigitoxoside (Mono-Dggenin) or digoxigenin (Dggenin) (Fig. 1), which were formed by the successive cleavage of the sugar moiety, as well as with endogenous digitalis-like immunoreactive substances (DLIS).2) These cause a false-elevation or -lowering of the serum Dg concentration due to the inappropriate prescriptions of Dg dosages by physician. To overcome this problem, Ikeda et al. designed a new hapten of Dg and developed a radioimmunoassay (RIA) for Dg in human serum, which can clearly discriminate Dg from the Dg metabolites (Bis-Dggenin, Mono-Dggenin and Dggenin), but not DLIS.3) Liquid chromatography/mass spectrometry (LC/MS) also seems to be suitable for this purpose because of its high sensitivity, specificity and without interfering from DLIS. Recently, the determination of digitoxin or Dg using LC/MS has been reported, [4][5][6][7][8] but its application to real samples obtained from digitalized patients followed by comparison with the data obtained from immunoassay has only been done in our report for determining digitoxin. 4)In this study, we developed a determination method for Dg in human serum using stable isotope dilution LC/electrospray ionization (ESI)-tandem mass spectrometry (MS/MS) and applied this method to real samples. The data obtained in this study were compared to those obtained by using RIA with the anti-serum clearly discriminating Dg from its metabolites.3) Kakuma-machi, Kanazawa 920-1192, Japan: and b Faculty of Pharmaceutical Sciences, Hokuriku University; Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan. Received April 14, 2007 accepted June 12, 2007; published online June 18, 2007 A method for the determination of digoxin in human serum using a liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) technique is reported. Digoxin and the internal standard, [21,21,22-2 H 3 ]digoxin, were extracted from 250 m ml of human serum using a solid phase extraction cartridge (Oasis HLB) and analyzed by LC/ESI-MS/MS in the selected reaction monitoring mode. The intra-and interassay reproducibility and accuracy were satisfactory within the quantification range of 0.20-3.20 ng/ml. The concentrations of digoxin in the serum samples obtained from digitalized patients (n‫)91؍‬ were ...

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Section: Determination Of Dg In Sera Obtained From Digitalizedmentioning

confidence: 99%

Determination of Digoxin in Human Serum Using Stable Isotope Dilution Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry

Mitamura

Horikawa

Yamane

et al. 2007

Biological & Pharmaceutical Bulletin

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“…The levels are also elevated in plasma and urine from pregnant women (Graves et al 1984;Vinge & Ekman 1988a). Urinary digoxin-like immunoreactive substance increases progressively during pregnancy, but falls rapidly following parturition (Friedman et al 1987).…”

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Progesterone, some Progesterone Derivatives and Urinary Digoxin‐Like Substances from Pregnant Women in Radioimmuno‐ and ⁸⁶Rb‐Uptake Assays of Digoxin

Vinge

Helgesen-Rosendal

Bäckström

1988

Pharmacology & Toxicology

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Progesterone and some derivatives were tested in a radioimmunoassay (RIA) of digoxin and in a bioassay measuring the 86Rb-uptake into red blood cells as an index of Na+, K+-ATPase activity. The digitalis-like activity of the hormones was compared with that found in chromatographic fractions of material extracted from the urines of pregnant women at term. Progesterone at concentrations greater than 10(-6) M cross-reacted in the RIA, and at 10(-3) M it decreased 86Rb-uptake by 18%. The anaesthetic progesterone derivates 5 alpha-pregnane-3 alpha-ol-20-one and 5 alpha-pregnane-3,20-dione crossreacted to a lesser degree in the RIA and lacked effect in the bioassay. Similar results were obtained with pregnandiol-glucuronide, the major urinary metabolite of progesterone. In contrast, several fractions of the urinary material had significant effects in both assays. It is concluded that the digitalis-like activity of progesterone is not coupled to properties associated with its anaesthetic effects. Furthermore, although progesterone may account for a part of the endogenous digoxin-like substances in serum of neonates and pregnant women, neither progesterone proper nor pregnandiol-glucuronide explains the great amount of digoxin-like substances found in the urines.

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Endogenous factors with immunological and biological activity similar to cardiac glycosides: Biochemical and pathophysiological implications

Clerico

Mariani

1992

J Endocrinol Invest

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Urinary digoxin-like immunoreactive substance in pregnancy

Cited by 9 publications

References 18 publications

Determination of Digoxin in Human Serum Using Stable Isotope Dilution Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry

Determination of Digoxin in Human Serum Using Stable Isotope Dilution Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry

Progesterone, some Progesterone Derivatives and Urinary Digoxin‐Like Substances from Pregnant Women in Radioimmuno‐ and ⁸⁶Rb‐Uptake Assays of Digoxin

Endogenous factors with immunological and biological activity similar to cardiac glycosides: Biochemical and pathophysiological implications

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Urinary digoxin-like immunoreactive substance in pregnancy

Cited by 9 publications

References 18 publications

Determination of Digoxin in Human Serum Using Stable Isotope Dilution Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry

Determination of Digoxin in Human Serum Using Stable Isotope Dilution Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry

Progesterone, some Progesterone Derivatives and Urinary Digoxin‐Like Substances from Pregnant Women in Radioimmuno‐ and 86Rb‐Uptake Assays of Digoxin

Endogenous factors with immunological and biological activity similar to cardiac glycosides: Biochemical and pathophysiological implications

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Progesterone, some Progesterone Derivatives and Urinary Digoxin‐Like Substances from Pregnant Women in Radioimmuno‐ and ⁸⁶Rb‐Uptake Assays of Digoxin