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Fluorometrische Bestimmung von “aktiviertem” Cyclophosphamid und Ifosfamid im Blut

Fluorometric determination of “Activated” cyclophosphamide and ifosfamide in blood

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Summary

“Activated” N-(2-Chloroethyl)amido-oxazaphosphorines like 4-hydroxycyclophosphamide, 4-hydroperoxycyclophosphamide, 4-hydroxyifosfamide, and 4-hydroperoxyifosfamide can be determined fluorometrically by condensation of liberated acrolein with m-aminophenol yielding 7-hydroxychinolin. The method permits determination of 10-10 mol and is specific for “activated” N-(2-Chloroethyl)amido-oxazaphosphorine metabolites which liberate acrolein under conditions of the test. Neither cyclophosphamide nor ifosfamide or other metabolites of this cytostatics interfere with the test. Blood levels of free 4-hydroxycyclophosphamide and 4-hydroxyifosfamide were determined after injection of cyclophosphamide and ifosfamide into mice.

Zusammenfassung

“Aktivierte” N-(2-Cloräthyl)-amido-oxazaphosphorine wie 4-Hydroxycyclophosphamid, 4-Hydroperoxycyclophosphamid, 4-Hydroxyifosfamid und 4-Hydroperoxyifosfamid können über die Freisetzung von Acrolein und dessen Kondensation mit m-Aminophenol zu 7-Hydroxychinolin fluorometrisch bestimmt werden. Die Nachweisempfindlichkeit beträgt 1x10-10 mol; der Test ist spezifisch für “aktivierte” N-(2-Chloräthyl)-amidooxazaphosphorin-Metabolite mit aldehydogener Funktion am Kohlenstoff 4 des Oxazaphosphorin-Rings, welche unter Testbedingungen Acrolein freisetzen. Weder Cyclophosphamid oder Ifosfamid, noch andere Metabolite dieser Cytostatica stören den Test. Im Mäuseblut wurden die Spiegel von freiem 4-Hydroxycyclophosphamid und 4-Hydroxyifosfamid nach Injektion von Cyclophosphamid bzw. Ifosfamid in einem Zeitraum vom 90 min nach der Injektion bestimmt.

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Literatur

  • Alarcon, R.A.: Fluorometric determination of acrolein and related compounds with m-aminophenol. Anal. Chem.40, 1704–1708 (1968)

    Google Scholar 

  • Brock, N., Hohorst, H.J.: Über die Aktivierung von Cyclophosphamid in vivo und in vitro. Arzneim. Forsch. (Drug Res.)13, 1021–1031 (1963)

    Google Scholar 

  • Brock, N., Hohorst, H.J.: The problem of specificity and selectivity of alkylating cytostatics: Studies on N-2-chloro-ethyl-amido-oxazaphosphorines. Z.Krebsforsch.88, 185–215 (1977)

    Google Scholar 

  • Hohorst, H.J., Zieman, A., Brock, N.: 4-Ketocyclophosphamide, ametabolite of cyclophosphamide. Formation, chemical, and biological properties. Arzneim. Forsch. (Drug Res.)21, 1254–1257 (1971)

    Google Scholar 

  • Hohorst, H.J., Draeger, U., Peter, G., Voelcker, G.: The problem of oncostatic specificity of cyclophosphamide (NSC 26271): studies on the reactions that control the alkylating and cytotoxic activity. Cancer Treat. Rep.60, 309–315 (1976)

    Google Scholar 

  • Hohorst, H.J., Peter, G., Struck, R.F.: Synthesis of 4-hydroperoxy derivatives of ifosfamide and trofosfamide by direct ozonation and preliminary antitumor evaluation in vivo. Cancer Res.26, 2278–2281 (1976)

    Google Scholar 

  • Norpoth, K., Müller, G., Raidt, H.: Isolierung und Charakterisierung zweier Hauptmetabolite von Ifosfamid aus Patientenurin. Arzneim. Forsch. (Drug Res.)26, 1376–1377 (1976)

    Google Scholar 

  • Peter, G., Wagner, T., Hohorst, H.J.: Studies on 4-hydroperoxycyclophosphamide (NSC 181815): a simple preparation method and its application for the sythesis of a new class of “activated” sulfurcontaining cyclophosphamide (NSC-26271) derivatives. Cancer Treat. Rep.60, 429–435 (1976)

    Google Scholar 

  • Przybylski, M., Ringsdorf, H., Lenssen, U., Peter, G., Voelcker, G., Wagner, T., Hohorst, H.J.: Mass spectrometric characterization of activated N-(2-chloroethyl)amido oxazaphosphirine derivatives. Biomed. Mass Spectrom.4, 209–215 (1977)

    Google Scholar 

  • Takamizawa, A., Matsumoto, S., Inata, T., Tochino, Y., Katagiri, K., Yamaguchi, K., Shiratori, O.: Synthesis and metabolic behavior of the suggested active species of Isophosphamide having cytostatic activity. J. Med. Chem.17, 1237–1239 (1974)

    Google Scholar 

  • Voelcker, G., Draeger, U., Peter, G., Hohorst, H.J.: Studien zum Spontanzerfall von 4-Hydroxycyclophosphamid und 4-Hydroperoxycyclophosphamid mit Hilfe der Dünnschichtchromatographie. Arzneim. Forsch. (Drug Res.)24, 1172–1176 (1974)

    Google Scholar 

  • Voelcker, G.: Untersuchungen über Reaktionen von 4-Hydroxycyclophosphamid, einem Metaboliten des Cyclophosphamid und die Identifizierung von Cyclophosphamidmetaboliten in vivo. Inaugural-Diss. Fachbereich Biochemie und Pharmazie, Universität Frankfurt am Main 1976

  • Wagner, T., Peter, G., Voelcker, G., Hohorst, H.J.: Characterization and qualitativ estimation of activated cyclophosphamide in blood and urine. Cancer Res.37, 2592–2596 (1977)

    Google Scholar 

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Voelcker, G., Haeglsperger, R. & Hohorst, H.J. Fluorometrische Bestimmung von “aktiviertem” Cyclophosphamid und Ifosfamid im Blut. J Cancer Res Clin Oncol 93, 233–240 (1979). https://doi.org/10.1007/BF00964578

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