Michael D Harvey

Publications (3)2.97 Total impact

• Article: Development and validation of an LC-UV method for the quantification and purity determination of the novel anticancer agent C1311 and its pharmaceutical dosage form.

  Monique W J den Brok, Bastiaan Nuijen, Michel J X Hillebrand, Charles K Grieshaber, Michael D Harvey, Jos H Beijnen
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  ABSTRACT: C1311 (5-[[2-(diethylamino)ethyl]amino]-8-hydroxyimidazo [4,5,1-de]-acridin-6-one-dihydrochloride trihydrate) is the lead compound from the group of imidazoacridinones, a novel group of rationally designed anticancer agents. The pharmaceutical development of C1311 necessitated the availability of an assay for the quantification and purity determination of C1311 active pharmaceutical ingredient (API) and its pharmaceutical dosage form. A reversed-phase liquid chromatographic method (RP-LC) with ultraviolet (UV) detection was developed, consisting of separation on a C18 column with phosphate buffer (60 mM; pH 3 with 1 M citric acid)-acetonitrile-triethylamine (83:17:0.05, v/v/v) as the mobile phase and UV-detection at 280 nm. The method was found to be linear over a concentration range of 2.50-100 microg/mL, precise and accurate. Accelerated stress testing showed degradation products, which were well separated from the parent compound, confirming its stability-indicating capacity. Moreover, the use of LC-MS and on-line photo diode array detection enabled us to propose structures for four degradation products. Two of these products were also found as impurities in the API and more abundantly in an impure lot of API.
  Journal of Pharmaceutical and Biomedical Analysis 10/2005; 39(1-2):46-53. · 2.97 Impact Factor
• Source

  Available from: uu.nl

  Article: Compatibility and stability of the novel anti-cancer agent C1311 in infusion devices and its in vitro biocompatibility.

  Monique W J den Brok, Bastiaan Nuijen, Remko Harms, Josie N Buluran, Michael D Harvey, Charles K Grieshaber, Jos H Beijnen
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  ABSTRACT: C1311 is the lead compound from the imidazoacridinones, a novel group of rationally designed anti-cancer agents. The compound is pharmaceutically formulated as a lyophilized product containing 100 mg C1311 (anhydrous free base) per dosage unit and requires reconstitution before intravenous administration. The aim of this study was to determine the stability of C1311 in the reconstituted solution and infusion solution and its compatibility with infusion devices. Moreover, the buffer capacity and haemolytic potential of C1311 infusion solutions, which exhibit a relatively low pH of 2-3, were evaluated in vitro. C1311 was shown to be stable in the reconstituted solution for at least 48 h and for at least 96 h after subsequent dilution in 0.9% sodium chloride and 5% dextrose. In vitro infusion simulation studies showed C1311 infusion solutions to be compatible with a low-density polyethylene administration set. Furthermore, the buffer capacity and haemolysis studies showed no indications for haemolysis or potential for vascular irritation upon continuous infusion of C1311. In conclusion, C1311 lyophilized product is adequately stable and compatible after reconstitution and in infusion fluids to be used in the clinic and is not expected to cause formulation-associated side effects in the intended administration schedule in the forthcoming Phase I clinical study.
  Journal of Oncology Pharmacy Practice 04/2005; 11(1):13-9.
• Source

  Available from: uu.nl

  Article: Pharmaceutical development of a parenteral lyophilised dosage form for the novel anticancer agent C1311.

  Monique W J Den Brok, Bastiaan Nuijen, J Jantina Kettenes-Van Den Bosch, M J Van Steenbergen, Josie N Buluran, Michael D Harvey, Charles K Grieshaber, Jos H Beijnen
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  ABSTRACT: C1311 (5-[[2-(diethylamino)ethyl]amino]-8-hydroxyimidazo [4,5,1-de]-acridin-6-one-dihydrochloride trihydrate) is the lead compound from the group of imidazoacridinones, a novel group of rationally designed anticancer agents. C1311 shows significant cytotoxic activity in vitro and in vivo toward a range of colon tumours. The aim of the present study is to develop a sterile and stable, injectable pharmaceutical product for C1311 to be used in phase I clinical trials. C1311 drug substance was structurally and analytically characterised by chromatographic, spectrometric, and diffraction techniques. C1311 was freely soluble in water, and its stability was investigated in several liquid and lyophilised formulations with or without the use of buffering, tonicity, and bulking agents. The final product, containing 100 mg/vial C1311 (as anhydrous free base), was stable for at least 3 months under accelerated storage conditions and at the designated long-term storage condition of 5 +/- 3 degrees C in the dark. The drug is currently used in phase I clinical trials.
  PDA journal of pharmaceutical science and technology / PDA 59(5):285-97.