Hplc Separation Of Positional Isomers Of Trifluorophenylacetic Acid And Its Starting Material

Trifluorophenylacetic acid (TFPAA) was synthesized from 2,4,5-trifluorophenyl bromide and malonic acid starting materials as part of process development for a pharmaceutical intermediate. Impurity profile methods, sensitive to positional isomers, have been developed for 2,4,5-trifluorophenyl bromide and 2.4.5-TFPAA. The HPLC impurity profile method for 2.4.5-TFPAA was validated consistent with ICH guidelines. An HPLC weight percent assay method was also developed and validated for 2,4,5-TFPAA. Residual malonic acid in 2,4,5-TFPAA was determined with a weight percent method by GC. Non-positional isomer impurities in 2,4.5TFPAA were identified by LC-MS.