Lack of metabolic racemisation of ropivacaine, determined by liquid chromatography using a chiral AGP column

Ropivacaine hydrochloride monohydrate (ropivacaine) is a new local anaesthetic agent which is administered exclusively as the (-)-(S)-form. The aim of the study was to determine whether metabolic racemisation of (-)-(S)-ropivacaine occurs. This was tested in man, rat, dog, and sheep after different routes of administration. The enantiomers of ropivacaine 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 ropivacaine and the two major metabolites. In the samples examined, no trace of metabolic racemisation was observed. In pharmacokinetic, pharmacodynamic, toxicological, and metabolic studies, therefore, nonchiral assays are considered to be adequate.