Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.770019
Title: The physicochemical and biological stability of Trabectedin, Epirubicin & Cyclophosphamide in the administering device(s) under standard clinical practice conditions
Author: Lahsini, Imane
ISNI:       0000 0004 7660 6324
Awarding Body: Kingston University
Current Institution: Kingston University
Date of Award: 2018
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Abstract:
Most anti-cancer drugs are licensed for use with a limited amount of stability data, which does not fully cover the needs of oncology practice. Consequently, this has created a need for healthcare professionals to generate more data on the stability and compatibility of various drug regimens, as well as their interactions with drug containers to endure that patients receive the best possible care. This research concentrates upon two chemotherapeutic regimens. The physicochemical stability of Trabectedin in elastomeric pumps was assessed after storage at 25°C +/-1°C and 37°C under light conditions. A stability-indicating Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) method for the analysis of Trabectedin at the clinically relevant dosage was developed and validated. The next study involved the investigation of the compatibility of Epirubicin and Cyclophosphamide (EC drugs), when stored together in IV infusion bags and elastomeric pumps at 4°C and 25°C +/-1°C with protection from light. Analysis was carried out by LC-MS/MS and Nuclear Magnetic Resonance NMR. The effect of storage on the "cell-killing" efficacy of Trabectedin and EC drugs on established human cancer cell lines was also investigated. Cytotoxic efficacy of each drug regimen was tested immediately after the drugs reconstitution and at intervals during the period of analysis, by exposing the human cancer cells to the final drugs dilution. Results showed that at 37°C Trabectedin degradation occurred over 37% of the original concentration following 8 days storage with a 95% level of confidence. If the temperature of the elastomeric infusion pumps is controlled at no higher than 25°C. Trabectedin can be prepared and stored for up to 8 days. The best results from EC stability/compatibility test revealed that Epirubicin and Cyclophosphamide are not stable in the same infusion solution after being mixed together. The results also revealed that Trabectedin retained its full potency for 10 hours after reconstitution. Cyclophosphamide did not show any inhibition of cell growth when it was added directly to target cells without prior vivo activation, whereas Epirubicin retained its cytotoxic potency for 3 days after the drugs storage in both the elastomeric infusion pumps and IV bags. Although the biological stability of anticancer drugs is a very useful assay, this study shows it may not correlate completely with the physicochemical stability of the drugs.
Supervisor: Barton, Stephen ; Swinden, Julian ; Nabhani, Shereen Sponsor: Government of Morocco
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.770019  DOI: Not available
Keywords: Biological sciences
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