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The stability of methotrexate solutions, subject to a freeze-thaw procedure, has been investigated. According to our results these solutions can be produced in batches in the hospital pharmacy and thawed to room temperature immediately before use without any degradation of methotrexate within the time limits given. I N T R O D U C T I O NThe handling of cytotoxic agents used in cancer therapy will often give rise to hazards which ought to be avoided. When such drugs are to be administered by intravenous infusion, it is preferable that the drug solution should be prepared under controlled conditions in the hospital pharmacy, rather than under normal conditions on the ward. The advantages of a centralized intravenous additive service include a lower risk of microbial contamination of the fluids (1,2), a reduced likelihood of medication, calculation and compounding errors as well as greater safety for the technician preparing the solutions.The preparation of a single intravenous admixture, as required for individual patients, is a labour-intensive operation. Series-production of intravenous solutions, containing drug additives at concentrations in regular use, would be of greater advantage. For cytotoxic intravenous solutions, batch production performed a limited number of times throughout the year would also mean increased safety for the personnel handling the cytotoxic compounds. The solutions produced can then be stored in a freezer, and thawed in a microwave oven to body temperature when needed. This procedure has been investigated and has been applied to several antibiotics in solution (3-5). This procedure, however, cannot be generalized to all intravenous infusion solutions and additives. Every new compostion of a solution will have to be investigated separately before the freeze-thaw method can be applied to the product. In a previous short communication (6) we reported some preliminary results on the additives, methotrexate and adriamycine. In this report a thorough investigation has been made of the stability of methotrexate following the usual handling of this compound on the ward, exposure tTo whom correspondence should be addressed.

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