The Synthesis of an Internal Standard for Bicalutamide

(R,S)-Bicalutamide [N-(4-cyano-3-trifluoromethylphenyl)-α-methyl-α-hydroxy-β-(4- fluorophenylsulfonyl)propanamide], sold as Casodex®, is the leading antiandrogen currently used to treat prostate cancer. It binds to androgen receptors and blocks cancer growth. This work aims to develop internal standards for the bio-analytical component of clinical trials that are required to detect bicalutamide and derivatives. An internal standard is added to the body fluid sample (mostly blood) at the beginning of the sample work up at about the same concentration of the analyte to be quantified. An ideal internal standard has a similar extraction recovery and a similar retention time in HPLC. For quantification with mass spectrometry it should have a difference of at least 3 mass units from the analyte and a similar ionization response. The internal standard is used to calibrate the total ion current of the metabolite.