A novel LC–MS/MS analytical method for detection of articaine and mepivacaine in blood and its application to a preliminary pharmacokinetic study

Abstract

Local anaesthetics (LAs) are commonly used in surgery, especially in dentistry. They cause a transitory inhibition of nerve signal due to the blockade ofthe voltage-gated sodium channels. LAs are administrated alone or with vasoconstriction agents, such as adrenaline. Toxicity of LAs is associated to neurological and cardiovascular alterations. Tachycardia, arrhythmia, tremors, tonic-clonic seizure and respiratory depression (at high doses) are the main symptoms of intoxication by LAs. Lidocaine, articaine and mepivacaine are among the most used anaesthetics. This study aimed to fully validated a new method for the simultaneous detection of articaine and mepivacaine in whole blood. Sample treatment consisted in a liquid-liquid extraction with phosphate buffer (pH 8, 0.1 M) and ethyl-acetate. Analysis was performed by liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode (transitions: articaine, 285→8658 m/z; mepivacaine, 247→9870 m/z; lidocaine – internal standard –, 235→8658 m/z). The method proved to be highly sensitive with limit of quantifications for articaine and mepivacaine of 0.8 and 0.1 ng/mL, respectively. Accuracy and precision were always within the acceptance criteria. The new procedure was also successfully applied to a preliminary pharmacokinetics study.