Determination of vecuronium in blood by HPLC with UV and electrochemical detection: a pilot study in man.

Vecuronium bromide is a non-depolarizing neuromuscular blocking agent with a rather low therapeutic level. Rapid, sensitive, and selective determination of vecuronium bromide in human blood or plasma was essential for pharmacokinetic study. We developed such a method using HPLC with electrochemical detection. Samples were first acidified, followed by a one-step liquid-liquid extraction. Tubocurarine, which has a structure similar to that of vecuronium, was used as the internal standard. The electrochemical detector, Ag/AgCl electrodes, was operated by setting the working electrodes, W1 and W2, at +0.65 V and +1.05 V, respectively. When vecuronium blood concentration was plotted versus peak area ratios (PAR) of vecuronium over tubocurarine, a linear relationship was observed over the range of 25 ng/mL to 500 ng/mL with a correlation coefficient greater than 0.997. Clinically possible sources of interference, such as atropine, apresoline, droperidol, fentanyl, labetalol, thiopentone, atracurium, and valium, were examined and none showed interference in the assay of vecuronium and tubocurarine. This method has been successfully applied in a preliminary study of the pharmacokinetics of vecuronium in a patient undergoing surgery. The low detection limit of this method in the patient was 3 ng/mL.