Issue Date: December 7, 2015
A few years back, researchers who thought they were conducting studies with Pfizer’s selective kinase inhibitor bosutinib got an unwanted surprise. Numerous chemical suppliers were selling material labeled bosutinib that turned out to be an isomer of the compound. The revelation that these researchers were unwittingly using a compound that was not, in fact, bosutinib threatened to invalidate numerous research studies. To help scientists avoid such mishaps with bosutinib in the future, chemists at Pfizer, led by Frank R. Busch, are reporting simple analytical procedures that distinguish genuine bosutinib—now approved as the leukemia drug Bosulif—from its isomers. The new procedures also provide analyses of the pertinent synthetic precursors (Org. Process Res. Dev. 2015, DOI: 10.1021/acs.oprd.5b00244). For chemists making bosutinib, the Pfizer group exhaustively characterized and compared all likely isomers of the cyanoacetamide starting material. They then compared bosutinib and its possible isomers using HPLC and infrared spectroscopy and by melting point. They concluded that although bosutinib and its isomers are distinguishable in these analyses, it still behooves researchers to use multiple techniques or a standard to ensure they are working with genuine bosutinib.
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