Determination of free concentrations of ropivacaine and bupivacaine in plasma from neonates using small-scale equilibrium-dialysis followed by liquidchromatography-mass spectrometry

Attempts to determine a safe plasma concentration of ropivacaine and bupiva caine in neonates have not been consistent. This might be due to an underes timation of free drug in small plasma samples by currently used techniques, e.g., ultrafiltration. We describe a simple microscale equilibrium-dialysi s technique for the separation of free and bound ropivacaine and bupivacain e. The free drug in the dialysate was determined using solid-phase extracti on and liquid chromatography with mass spectrometry. Pentycaine was used as an internal standard and added to the dialysates prior to extraction. The method is very selective and sensitive, as no compounds other than the anal yte and internal standard were observed in the resulting chromatograms at l ow ng/ml levels. The limit of quantitation was 2.5 ng/ml. The calibration c urve was linear in the range of 2 to 1000 ng/ml. The precision of the whole procedure was 8.1% (n=10) and 6.5% (n=7) for ropivacaine and bupivacaine, respectively. The method was tested in the analysis of plasma samples taken from neonates who had received epidural injections. (C) 2000 Elsevier Scie nce BN. All rights reserved.