In clinical use for over sixty years, methotrexate is a well known antineoplastic drug that targets increased intracellular levels of the enzyme dihydrofolate reductase, resulting in the arrest of cell proliferation for several acute human leukemias, chlorocarcinoma, osteogenic sarcoma, and a variety of head and neck carcinomas. Subsequently, methotrexate has demonstrated utility for treatment of a variety of other disorders, such as psoriasis, Wegner's granulomatosis, sarcoidosis, and rheumatoid arthritis. Because of the potential for overdose, therapeutic drug monitoring is required to identify patients with poor drug absorption, unusual metabolism or clearance, changes in bioavailability, or saturation, and to prevent drug-induced toxicity. We describe here an improved, reproducible process for the synthesis of a fluorescent methotrexate conjugate which resulted in a fifty-fold improvement in yield over the prior manufacturing process, and confirmation of the structure of the conjugate by comparison with materials prepared from protected methotrexate derivatives.

Development of a process for methotrexate conjugate synthesis

243rd National Meeting (2012)

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