Dahlia Salman

Effect of environmental conditions on performance of elastomeric pumps

With the advent of ambulatory infusion devices, home-based chemotherapy services are feasible for both adult and pediatric populations. Home chemotherapy not only reduces the cost of treatment, it also optimizes the pharmacy services and improves patients’ quality of life.[1][1],[2][2] Studies

Improving the stability of anticancer drugs

In practice, oncology pharmacists are often faced with the challenge of optimizing therapy for patients with the constraints of available pharmacy resources. Centralized preparation of infusions on the day can contribute to delays and increased patient wait times. However, if made in advance or outsourced, this can have a positive impact on all stakeholders. Unfortunately, stability studies are often limited. In the recent published guidelines on the practical stability studies of anticancer drugs, the authors highlighted a need for additional stability data covering practical uses of anticancer drugs. Often, the available data published by the manufacturer do not reflect the true stability of the drugs. The manufacturer usually quotes the stability of anticancer drugs after the dilution step as being stable for 8 to 12 h for bacterial contamination despite the fact that these anticancer drugs are normally prepared in centralized units under strict aseptic environment. Therefore, performing stability studies on cytotoxic drugs will utilize more data on their stability profile and allow preparation for the weekend or for the whole home chemotherapy treatment cycle in advance and consequently reduce the cost for cancer centres. Improving the stability profile of chemotherapeutic agents can help pharmacists to streamline services and to offer patients a less disruptive regimen which can translate into better quality of life. We read with interest the recently published article ‘Long-term stability of clofarabine injection concentrate and diluted clofarabine infusion solution’. It is always interesting to read a stability study of an anticancer drug and observe the storage conditions for the test solutions that will mimic normal clinical practices. It is important to note that these clinical practices will vary from one country to another as some countries’ room temperature could exceed 30 C depending on the climate of the country and the air-conditioning facilities available at each hospital. In addition, anticancer drugs could be provided to patients via portable elastomeric pumps to facilitate home chemotherapy. These pumps will be exposed to a temperature higher than ambient up to or exceeding 37 C as it will be worn by the patients and covered by their clothes. This higher unknown temperature could cause degradation of the anticancer drug and cause undesirable materials to be leached to the solution from the administering devices/ containers. Therefore, the temperature at which these chemotherapeutic agents are exposed to needs to be considered. Stability studies need to be performed for each anticancer drug while stored at the in-use conditions as cytotoxic drugs are known to have a narrow therapeutic range so it is essential to provide patients with the right dose for a successful treatment. We would like to share our recent ongoing investigation in dealing with the use of elastomeric pumps to achieve home chemotherapy. This will allow us to determine the stability of the anticancer drug at these different temperatures to mimic standard clinical practices including home chemotherapy. In addition, the duration that the anticancer drug is in contact with the administering devices/containers will be considered for each anticancer drug individually. Ultimately, performing stability studies of cytotoxic drugs taking into account the actual room temperature of the hospitals or cancer research center is critical.

Evaluation of the stability profile of anticancer drugs: A review of Ifosfamide and Mesna regimen for the treatment of metastatic soft tissue sarcoma.

Purpose This paper aims to summarise and critically review the existing published literature with regard to clinical considerations as well as stability testing studies of Ifosfamide and Mesna. It also aims to highlight the factors that should be considered when designing and conducting stability testing experiments. Summary Ifosfamide and Mesna are currently given to patients for 14 days continuous home-based infusion for the treatment of soft tissue sarcoma. No previous work has evaluated their stability for more than 7 days under real-life conditions so the current regimen involves patients visiting hospital twice during the 14-day treatment. This may create extra disruption to patients’ life style as well as increasing the workload for cancer services. Conclusion There is a need to conduct stability testing experiments for Ifosfamide and Mesna taking into consideration all of the highlighted factors to mimic standard clinical practice.

Evaluation of the performance of elastomeric pumps in practice: are we under-delivering on chemotherapy treatments?

Abstract Background and aims: Elastomeric pumps are widely used to facilitate ambulatory chemotherapy, and studies have shown that they are safe and well received by patients. Despite these advantages, their end of infusion time can fluctuate significantly. The aim of this research was to observe the performance of these pumps in real practice and to evaluate patients’ satisfaction. Methods: This was a two-phase study conducted at three cancer units over 6 months. Phase-1 was an observational study recording the status of pumps at the scheduled disconnection time and noting remaining volume of infusion. Phase-2 was a survey of patients and their perception/satisfaction. Ethical approval was granted. Results: A total of 92 cases were observed covering 50 cases disconnected at hospital and 42 disconnected at home. The infusion in 40% of hospital disconnection cases was slow, with patients arriving at hospital with unfinished pumps; 58% of these had an estimated remaining volume which exceeded 10 mL with 35% exceeded 20 mL. In 73% of these cases, and regardless of the remaining volume, the patient was disconnected and the pump was discarded. Conclusions: The performance of pumps varied, which affected nurse workload and patients’ waiting-times. A smart system is an option to monitor the performance of pumps and to predict their accuracy.

New investigations into the stability of Mesna using LC-MS/MS and NMR.

Introduction: It is important for sarcoma patients to receive the correct dose of Mesna as an adjuvant with ifosfamide to reduce the risk of hemorrhagic cystitis. This paper describes a study conducted to evaluate the physicochemical stability of Mesna for injection formulation over 14 days. Methods: Mesna samples (n = 4, 20 mg/ml) were incubated in glass vials at 37 + 0.5ºC. Mesna concentrations were determined by liquid chromatography-mass spectrometry (LC-MS/MS), and nuclear magnetic resonance spectroscopy (NMR) was used to detect degradation products. Evaporative losses and pH were also monitored. Results: Our results differed from those published in existing literature. Both LC-MS/MS and NMR indicated that Mesna was unstable. The mean percentage decrease in Mesna concentration was 40% by day 14 of the analysis. The presence of Mesna’s dimer Dimesna was detected on day 0 and its concentration increased over time. Dimesna was the only by-product identified. Conclusion: Both LC-MS/MS and NMR analyses confirmed the instability of Mesna and its conversion into Dimesna.

HPLC & NMR-based forced degradation studies of ifosfamide: The potential of NMR in stability studies

PURPOSE The aim of this study is to conduct a forced degradation study on ifosfamide under several stress conditions to investigate the robustness of the developed HPLC method. It also aims to provide further insight into the stability of ifosfamide and its degradation profile using both HPLC and NMR. METHODS Ifosfamide solutions (20mg/mL; n=15, 20mL) were stressed in triplicate by heating (70°C), under acidic (pH 1 & 4) and alkaline (pH 10 & 12) conditions. Samples were analysed periodically using HPLC and FT-NMR. RESULTS AND DISCUSSION Ifosfamide was most stable under weakly acidic conditions (pH 4). NMR results suggested that the mechanism of ifosfamide degradation involves the cleavage of the PN bond. For all stress conditions, HPLC was not able to detect ifosfamide degradation products that were detected by NMR. CONCLUSION These results suggest that the developed HPLC method for ifosfamide did not detect the degradation products shown by NMR. It is possible that degradation products co-elute with ifosfamide, do not elute altogether or are not amenable to the detection method employed. Therefore, investigation of ifosfamide stability requires additional techniques that do not suffer from the aforementioned shortcomings.