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.

Depth to mate and the 50-move rule

The most popular endgame tables (EGTs) documenting ‘DTM’ Depth to Mate in chess endgames are those of Eugene Nalimov but these do not recognise the FIDE 50-move rule ‘50mr’. This paper marks the creation by the first author of EGTs for sub-6-man (s6m) chess and beyond which give DTM as affected by the ply count pc. The results are put into the context of previous work recognising the 50mr and are compared with the original unmoderated DTM results. The work is also notable for being the first EGT generation work to use the functional programming language HASKELL.