Research paper
An HPLC and spectrophotometric study of the hydrolysis of ICRF-187 (dexrazoxane, (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane) and its one-ring opened intermediates

https://doi.org/10.1016/0378-5173(94)90303-4Get rights and content

Abstract

The hydrolysis of the cardioprotective agent dexrazoxane ICRF-187 ((+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane) and its one-ring open intermediates has been examined over a wide pH range using both HPLC and spectrophotometric methods. The isolation of these one-ring open intermediates by HPLC allowed a study of their hydrolysis reactions to be carried out spectrophotometrically without interference from other competing hydrolysis reactions. In 40 mM NaOH (25°C) the half-life for the hydrolysis of ICRF-187 is 0.3 h, at pH 7.4 (37°C) 9.3 h and in 1.0 M HC1 (25°C) 560 h. However, at pH 7.4 (37°C) the half-time for the production of the fully ring-opened hydrolysis product, which is presumably the active metal ion binding form of the drug, is 28 h. A full kinetic analysis was carried out within a reaction scheme that included both parallel and consecutive reaction steps and allowed the determination of the individual ring-opening reaction rate constants.

References (18)

There are more references available in the full text version of this article.

Cited by (38)

  • Interface-free capillary electrophoresis-mass spectrometry system with nanospray ionization—Analysis of dexrazoxane in blood plasma

    2016, Journal of Chromatography A
    Citation Excerpt :

    It should be noted that for analysis of dexrazoxane and its metabolite the ammonium cations must be added in the form of a salt to sustain acidic (or neutral) pH of the solution. Addition of ammonia would increase pH resulting in dramatic increase of the dexrazoxane hydrolysis during the sample storage and handling [36]. We have observed that the ADR-925/Dexrazoxane ratio was shifted within 7 analyses (70 min) more than 5 times towards the ADR-925.

  • Hydrophilic interaction liquid chromatography in the separation of a moderately lipophilic drug from its highly polar metabolites-the cardioprotectant dexrazoxane as a model case

    2011, Journal of Chromatography A
    Citation Excerpt :

    1H NMR (300 MHz, DMSO, Varian Mercury-Vx BB 300 instrument): δ 7.71 (1H; s; NH2); 7.49 (1H; s; NH2); 7.25 (1H; s; NH2); 7.15 (1H; s; NH2); 3.31–3.07 (9H; m; 4× CH2, CH); 2.92–2.85 (1H; m; CH2); 2.68–.61 (1H; m; CH2); 0.90 (3H; d; J = 6.5 Hz); 13C NMR (75 MHz, DMSO): δ 173.4; 173.1; 172.9; 172.5; 57.6; 55.6; 55.2; 54.4; 53.6; 53.3; 12.9. A mixture containing intermediates B and C was prepared by alkaline hydrolysis as described previously [19]. After quenching the hydrolysis, the presence of the intermediates was tested by direct infusion of the diluted sample solution (approx. 2 μg/mL) into the ESI–MS source. [

  • High-performance liquid chromatographic methods for the determination of topoisomerase II inhibitors

    2001, Journal of Chromatography B: Biomedical Sciences and Applications
  • Dexrazoxane (ICRF-187)

    1999, General Pharmacology
View all citing articles on Scopus

Tel. (204)-474-8325; Fax: (204)-275-7509.

View full text