Development and application of a quantitative LC-MS/MS assay for the analysis of four dental local anesthetics in human plasma and breast milk

Local anesthetics (LAs: articaine, lidocaine, bupivacaine, and mepivacaine) are essential for dental pain management. However, there are concerns that the lipophilic LAs could cross into breast milk causing toxicity to the infant. Our objective was to establish a multi-analyte LC-MS/MS method for the concurrent quantification of local anesthetics (LAs) in human plasma and breast milk, clarifying the transfer of LAs from plasma to breast milk, thereby offering crucial data for the safe assessment of LAs during the nursing period. Sample preparation for plasma and breast milk involved protein precipitation and a single dilution step. The chromatographic analysis was conducted using an ACQUITY UPLC BEH C18 column. Detection was facilitated by a triple quadrupole mass spectrometer employing positive electrospray ionization. The method demonstrated excellent linearity for articaine, mepivacaine, and bupivacaine across the range of 0.5 to 500 ng/mL, and for lidocaine from 1.0 to 1000 ng/mL in both plasma and breast milk, with correlation coefficients (R2) of 0.99 or higher. The method was effectively utilized in the analysis of samples from three nursing mothers who received dental treatment involving LAs. Articaine and lidocaine excretion in milk was confirmed, but it presented no significant safety risks to the breastfed infants.