Highly sensitive bioassay of lidocaine in human plasma by high-performance liquid chromatography-tandem mass spectrometry

A very sensitive HPLC-tandem mass spectrometric (LC-MS-MS) method for assaying lidocaine in human plasma was set up and fully validated. Lidocaine and an internal standard (bupivacaine) were extracted from 1 ml of alkalinized plasma with tert.-butylmethyl ether, back-extracted to a H3PO4 acidified solution and injected into a C-18 column. Acetonitrile-26 mmol/l ammonium acetate, pH 4.5 (70:30, v/v) was the mobile phase at a flow-rate of 1 ml/min. The effluent was detected by PE Sciex API 365 LC-MS-MS system in positive ion mode. Ionisation was performed using an atmospheric pressure chemical ionization ion source operating at 400 degrees C. The multi reaction monitoring transition 235-->86 was monitored. Linearity was ascertained in the 0.2-30 ng/ml range with a limit of quantitation of 0.2 ng/ml. Intra- and inter-assay precision and accuracy were less than or equal to 3.8%. The high sensitivity and specificity achieved by the method allowed concentrations of lidocaine to be measured in plasma of healthy subjects topically treated with lidocaine (5% ointment) on normal skin over a 32-h period after dosing. (C) 1999 Elsevier Science B.V. All rights reserved.