Simultaneous determination of remifentanil, etomidate, and rocuronium in serum microsamples from maternal or umbilical blood

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Abstract Purpose This study aimed to establish and validate an analytical method to accurately determine the anesthetics remifentanil, etomidate, and rocuronium simultaneously in extremely small volumes of serum from maternal or umbilical blood. Methods A microsample of serum (10 µl) was diluted up to 50 µl with pure water, then total protein was precipitated using acetonitrile, and the three anesthetics were determined using liquid chromatography-tandem mass spectrometry within 4 min. Mass spectrometry was performed with positive electrospray ionization in multiple reaction monitoring mode. The analytical method was characterized in terms of linearity, lower limit of quantification, accuracy, precision, and carry-over effects. The method was validated on samples from 20 pairs of newborns and their mothers. Results For all three anesthetics, the analytical method showed linearity (R² > 0.99), inter- and intra-day imprecision < 15% and carry-over < 5%. The lower limits of quantitation were 0.15 ± 0.02 ng/ml for remifentanil, 16.87 ± 0.51 ng/ml for etomidate, and 106.73 ± 8.63 ng/ml for rocuronium. Respective mean concentrations of each anesthetic in serum from maternal arteries, umbilical veins and umbilical arteries were as follows: remifentanil, 4.75 ± 0.19, 2.43 ± 0.13, and 1.33 ± 0.15 ng/ml; etomidate, 412.71 ± 35.29, 302.15 ± 29.03, and 166.24 ± 21.53 ng/ml; and rocuronium, 7.08 ± 0.48, 0.86 ± 0.16, and 0.44 ± 0.77 µg/ml. Respective rates of transport into placenta for the three anesthetics were 0.52 ± 0.02, 0.75 ± 0.04, and 0.13 ± 0.02 (all P < 0.001). Conclusion Our analytical method can accurately and reliably determine remifentanil, etomidate, and rocuronium simultaneously in microvolumes of maternal and umbilical serum, making it suitable for pharmacokinetic studies.