Process Development, Impurity Control, and Production of a Novel Tubulin Inhibitor

Abstract

Process development and production of a novel tubulin inhibitor are described. The desired API was obtained through selective iodination of the 12′ position of vinblastine and subsequent thiomethylation. Most of the impurities were identified, and process parameters were adjusted to control such impurities. The optimized process was scaled up under cGMP conditions to afford 230 g of the desired API.

Noneffervescent Method for Catalysis-Based Palladium Detection with Color or Fluorescence

“…Alternatively, trace metals may be quantified by fluorometric or colorimetric methods that are more amenable to on-site operation . Palladium is a scarce but useful metal due to its high catalytic turnover numbers in many chemical reactions. , After palladium-catalyzed reactions are employed in pharmaceutical production, extensive purification must be employed to remove residual palladium, requiring analysis of trace palladium. − Current instrumentally intensive methods take a significant amount of time, on the order of days or even weeks, including transportation of samples, to quantify residual palladium, hindering progress during the purification process . To expedite this process, many groups have reported fluorometric or colorimetric methods to detect palladium, , some of which rely on the palladium(0)-catalyzed cleavage of an allylic C–O bond. − …”