The hospital pharmacist: an important contributor to improved patient safety in the hospital.

Injectable drugs are high-risk products and their reconstitution in hospital wards is a potential source of errors. Thus, in order to secure the reconstitution process and thereby improve safety, the pharmacy department of Lausanne University Hospital is focusing on developing ready-to-use forms (CIVAS). These preparations are compounded in controlled clean rooms and are analyzed prior to release. In the intensive care unit, amiodarone 12.5 mg/mL in glucose 5% is one of the high-risk preparations, which has led the pharmacy to develop a ready-to-use solution. To this end, a one-year stability study was initiated, and the preliminary results (after six months) are illustrated here. A stability-indicating HPLC method was developed and validated for monitoring the concentration of amiodarone. Batches were stored at 5 °C and 30 °C, which were analyzed immediately after preparation, after one, two, four and six months of storage. The pH and osmolality values were monitored at the respective time intervals. It was observed that after six months, all the results were within specifications. However, the pH values started to decrease after two months when amiodarone was stored at 30 °C. After six months, a degradation peak appeared on the chromatogram of these solutions, which suggested that amiodarone is more stable at 5 °C. The preliminary results obtained in this study indicated that injectable amiodarone solutions are stable for six months under refrigerated storage conditions. The study is ongoing.

Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors.

The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-gamma (IFN-gamma)-producing T lymphocytes. Here we show that dying tumor cells release ATP, which then acts on P2X(7) purinergic receptors from DCs and triggers the NOD-like receptor family, pyrin domain containing-3 protein (NLRP3)-dependent caspase-1 activation complex ('inflammasome'), allowing for the secretion of interleukin-1beta (IL-1beta). The priming of IFN-gamma-producing CD8+ T cells by dying tumor cells fails in the absence of a functional IL-1 receptor 1 and in Nlpr3-deficient (Nlrp3(-/-)) or caspase-1-deficient (Casp-1(-/-)) mice unless exogenous IL-1beta is provided. Accordingly, anticancer chemotherapy turned out to be inefficient against tumors established in purinergic receptor P2rx7(-/-) or Nlrp3(-/-) or Casp1(-/-) hosts. Anthracycline-treated individuals with breast cancer carrying a loss-of-function allele of P2RX7 developed metastatic disease more rapidly than individuals bearing the normal allele. These results indicate that the NLRP3 inflammasome links the innate and adaptive immune responses against dying tumor cells.

Stability of dobutamine 500 mg in 50 ml syringes prepared using a Central Intravenous Additive Service

Objectives A pharmacy Central Intravenous Additives Service (CIVAS) provides ready to use injectable medicines. However, manipulation of a licensed injectable medicine may significantly alter the stability of drug(s) in the final product. The aim of this study was to develop a stability indicating assay for CIVAS produced dobutamine 500 mg in 50 ml dextrose 1% (w/v) prefilled syringes, and to allocate a suitable shelf life. Methods A stability indicating high performance liquid chromatography (HPLC) assay was established for dobutamine. The stability of dobutamine prefilled syringes was evaluated under storage conditions of 4°C (protected from light), room temperature (protected from light), room temperature (exposed to light) and 40°C (protected from light) at various time points (up to 42 days). Results An HPLC method employing a Hypersil column, mobile phase (pH=4.0) consisting of 82:12:6 (v/v/v) 0.05 M KH2PO4:acetonitrile:methanol plus 0.3% (v/v) triethylamine with UV detection at λ=280 nm was specific for dobutamine. Under different storage conditions only samples stored at 40°C showed greater than 5% degradation (5.08%) at 42 days and had the shortest T95% based on this criterion (44.6 days compared with 111.4 days for 4°C). Exposure to light also reduced dobutamine stability. Discolouration on storage was the limiting factor in shelf life allocation, even when dobutamine remained within 5% of the initial concentration. Conclusions A stability indicating HPLC assay for dobutamine was developed. The shelf life recommended for the CIVAS product was 42 days at 4°C and 35 days at room temperature when protected from light.

Stability of micafungin sodium solutions at different concentrations in glass bottles and syringes

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