LACK OF METABOLIC RACEMIZATION OF ROPIVACAINE, DETERMINED BY LIQUID-CHROMATOGRAPHY USING A CHIRAL AGP COLUMN

Ropivacaine hydrochloride monohydrate (ropivacaine) is a new local ana esthetic agent which is administered exclusively as the (-)-(S)-form. The aim of the study was to determine whether metabolic racemisation o f (-)-(S)-ropivacaine occurs. This was tested in man, rat, dog, and sh eep after different routes of administration. The enantiomers of ropiv acaine and two of the major metabolites, 3-hydroxy-ropivacaine and 2', 6'-pipecoloxylidide (PPX), were determined in urine samples by liquid chromatography on a Chiral AGP column after liquid-liquid extraction. It was possible to detect <1% of the (+)-(R)-enantiomer of both ropiva caine and the two major metabolites. In the samples examined, no trace of metabolic racemisation was observed, In pharmacokinetic, pharmacod ynamic, toxicological, and metabolic studies, therefore, nonchiral ass ays are considered to be adequate. (C) 1995 Wiley-Liss, Inc.