IMPROVED CLEANUP PROCEDURE FOR THE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY OF BUPIVACAINE ENANTIOMERS IN HUMAN PLASMA AND ULTRAFILTRATE IN THE NANOGRAM PER MILLILITER RANGE

A clean-up procedure to obtain a minimal detectable concentration of 5 -10 ng bupivacaine enantiomer per milliliter human plasma is described . The procedure consists of precipitation of plasma proteins using ace tonitrile, followed by solid-phase extraction using a cyano column. Th e eluate is then made alkaline, and bupivacaine is extracted using n-h exane. After evaporation of n-hexane, the residue is redissolved in th e eluent used for HPLC analysis. The HPLC method has been described pr eviously. The minimal detectable concentrations using this method are ca. 8 and 10 ng/ml for R-(+)- and S-(-)-bupivacaine, respectively. For both enantiomers, r(2) is >0.995 over the range of 9.5-760 ng/ml enan tiomer.