New anthracycline glycosides obtained by the nitrous acid deamination of daunorubicin, doxorubicin and their configurational analogues.

Cassinelli, Giuseppe; Ballabio, Marzia; Arcamone, Federico; Casazza, Anna Maria; Podestà, A

doi:10.7164/antibiotics.38.856

Cited by 8 publications

(1 citation statement)

References 24 publications

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“…IDA has been developed in an effort to produce a more effective and less toxic anthracycline. Its chemical structure is derived from daunorubicin, i.e., the C‐4 methoxy group in the D ring of daunorubicin is substituted with a hydrogen atom 3. The chemical structures of these four compounds are reported in Fig.…”

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Trace determination of anthracyclines in urine: a new high‐performance liquid chromatography/tandem mass spectrometry method for assessing exposure of hospital personnel

Sottani

Tranfo²,

Bettinelli

et al. 2004

Rapid Comm Mass Spectrometry

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Health-care workers handling antineoplastic agents may be exposed to extremely low doses of these drugs. Very sensitive and specific analytical methods are therefore needed for biological monitoring. The aim of this study was to develop and validate a method for trace level determination of doxorubicin, epirubicin, daunorubicin and idarubicin in human urine, using epi-daunorubicin as an internal standard. Solid-phase extraction (SPE) was used for sample preparation. Urine samples were loaded onto Bond Elut C18 cartridges. The analytes were eluted in methylene chloride/2-propanol (1:1, v/v) and then evaporated to dryness. The residue was reconstituted with the mobile phase prior to high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) analysis. Quantitation of each analyte was performed using the multiple reaction monitoring (MRM) method. The urine assay was linear over the range 0.1-2.0 microg/L, with a lower limit of quantification (LLOQ) of 0.10 microg/L for doxorubicin and epirubicin, and 0.03 microg/L for daunorubicin and idarubicin. The respective limits of detection (LODs) were 0.04 and 0.01 microg/L. The precision and accuracy of the assay were determined on three different days. The within-series precision was found to be always less than 13.9% for all the analytes. The overall precision expressed as relative standard deviation (RSD) was always less than 10.6%. The recovery of anthracyclines was assessed at two concentrations of the range tested (0.1 and 2.0 microg/L) and it ranged from 87.7% (daunorubicin) to 102.0% (doxorubicin) and from 79.1% (daunorubicin) to 90.7% (idarubicin) for the lower and the higher level, respectively, with a RSD always less than 9.1%. The uncertainty of the present assay was also evaluated and the combined uncertainty was always less than 20% over all the days of the validation study. This is the first method that makes use of LC/MS/MS for the biological monitoring of occupational exposure to anthracyclines.

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confidence: 99%

Trace determination of anthracyclines in urine: a new high‐performance liquid chromatography/tandem mass spectrometry method for assessing exposure of hospital personnel

Sottani

Tranfo²,

Bettinelli

et al. 2004

Rapid Comm Mass Spectrometry

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Totalsynthese von Anthracyclinonen

Krohn

1986

Angewandte Chemie

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Die bemerkenswerten Antitumor‐Eigenschaften der Anthracyclin‐Antibiotica haben auch die Synthesechemiker auf den Plan gerufen und in den letzten Jahren zu intensiver Aktivität auf diesem Gebiet geführt. Wegen der oft extremen Toxizität wurden der Substanzklasse ursprünglich wenig Chancen eingeräumt. Es gelang aber, teils durch mikrobielle Methoden (neue Stämme, Mutanten), teils durch halbsynthetische Modifikationen, den schmalen Grat zwischen Toxizität und gewünschter Wirkung so zu verbreitern, daß die Anthracycline heute den ersten Platz bei der Behandlung von Krebserkrankungen einnehmen (über 20% Marktanteil). Wie hoch dabei die Anforderungen an moderne Cytostatica sind, zeigt die Tatsache, daß von über 600000 seit 1955 im Tiermodell getesteten Substanzen nur ca. 40 den Weg in die Klinik geschafft haben. Im klinischen Test befinden sich inzwischen auch einige totalsynthetische Anthracycline. Daß die Beschäftigung der Synthesechemie mit dieser Substanzklasse darüber hinaus auch allgemeine Fortschritte bei der Lösung regio‐ und stereochemischer Probleme linear anellierter Ringsysteme gebracht hat, wird diese Übersicht zeigen.

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Total Synthesis of Anthracyclinone [New Synthetic Methods (60)]

Krohn

1986

Angew. Chem. Int. Ed. Engl.

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The remarkable antitumor properties of anthracycline antibiotics have motivated synthetic chemists, and a large number of groups have been active recently in this field. Initially, there was very little hope for this class of substances due to their extreme toxicity. However, the dividing line between toxicity and desired pharmacological effect has broadened to such an extent, partly through microbiological methods (new strains, mutants) and partly through semisynthetic modifications, that today anthracyclines take number one place (over 20% of the market) in the chemotherapy of (human) cancer. The demands made on modern cytostatica are extremely high, as may be seen from the fact that of the more than 600000 drugs tested in animals, only about 40 are in clinical use. In the meantime, some anthracyclines obtained by total synthesis are also in clinical testing. In this review it will hopefully be demonstrated that all those concerned in the chemotherapeutic use of these substances have also contributed to the general progress made in the solution of regio-and stereochemical problems of linearly annelated ring systems.

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New anthracycline glycosides obtained by the nitrous acid deamination of daunorubicin, doxorubicin and their configurational analogues.

Cited by 8 publications

References 24 publications

Trace determination of anthracyclines in urine: a new high‐performance liquid chromatography/tandem mass spectrometry method for assessing exposure of hospital personnel

Trace determination of anthracyclines in urine: a new high‐performance liquid chromatography/tandem mass spectrometry method for assessing exposure of hospital personnel

Totalsynthese von Anthracyclinonen

Total Synthesis of Anthracyclinone [New Synthetic Methods (60)]

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