REVERSED-PHASE AND CHIRAL HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY OF BUPIVACAINE AND ITS ENANTIOMERS IN CLINICAL-SAMPLES AFTER CONTINUOUS EXTRAPLURAL INFUSION

A previously unreported coupled achiral-chiral high-performance liquid chromatographic method has been developed to assay the levels of bupivacaine and its enantiomers in plasma samples, after the local anaesthetic had been given as a continuous extrapleural intercostal nerve block for 4 days, to relieve postoperative pain following thoracotomy. The method has been used to determine maximum, individual enantiomer and steady state levels in conjunction with an assessment of whether accumulation of bupivacaine occurs. An off-line extraction sample preparation is involved before determination of the "total" levels and final sample clean-up on a cyanopropyl silica column prior to "heart cutting" of the bupivacaine peak to a Chiral-AGP column for assay of the enantiomeric ratio. For an initial 5 patient number the mean maximum level was 5.43-mu-g/ml against a reported toxic level of around 5-mu-g/ml, which was reached in 72 h and the S-enantiomer gave slightly increased concentrations over the R-enantiomer for which there is some evidence of higher toxicity.