Chirality in Drug Design and Development 第9章.pdf

9 Bioequivalency Determination of Racemic Drug Formulations: Is Stereospecific Assay Essential? Aziz Karim Takeda Pharmaceuticals North America, Inc., Lincolnshire, Illinois, U.S.A. Cherukury Madhu Pfizer, Inc., Ann Arbor, Michigan, U.S.A. Chyung Cook Baxter Healthcare, Round Lake, Illinois, U.S.A. 1. INTRODUCTION Chemical synthesis results in the formation of an optically inactive racemate containing an equal amount of two stereoisomers with identical physico- chemical properties but differing in their property to rotate the plane of polarized light: one enantiomer will rotate the plane in the right direction, (dextrorotatory, d or þ) while its antipode will rotate in the opposite direction with the same magnitude (levorotatory, l or ). This optical characteristic, however, does not reflect the three-dimensional configuration of the molecule. A preferred nomenclature system incorporating the three- dimensional configuration of the chiral molecule is based on assigning a priority to atoms attached to the racemic carbon according to the Cahn– Ingold–Prelog rules [1]. Prefixes R- (rectus) and S- (sinister) are assigned to the enantiomers on the basis of their absolute configuration. No relation- ships exist between t