Rapid UPLC-MS/MS method for the determination of sufentanil in human plasma and its application in target-controlled...

A rapid, selective and highly sensitive ultra-performance liquid-chromatography mass-spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of sufentanil in human plasma. Sufentanil was separated on an ACQUITY™ UPLC BEH C(18) column (50 mm × 2.1 mm, ID 1.7 μm) and analyzed in positive-ion (PI) electrospray-ionization (ESI) mode. The mobile phase (MP) consisted of acetonitrile:water (45:55, v/v) under isocratic conditions at a flow rate of 0.2 ml/min. Sufentanil and internal-standard (IS) fentanyl were eluted at 1.47 and 1.16 min, respectively, and their responses were optimized at the transitions m/z 387.2>238.0 and m/z 337.2>188.0, respectively. The calibration curve was linear over the range 0.071-4.56 ng/ml, with coefficients of determination >0.999. The accuracy and precision of the method were between 96.49% and 100.37% (RSD<9%), and the mean recovery of sufentanil was 84.08 ± 7.29%. The method was successfully applied to evaluate the predictive accuracy of Gepts pharmacokinetic sets in a target-controlled infusion (TCI) model, and the Gepts parameters were capable of predicting sufentanil plasma concentrations when multi-level target concentrations were acquired during surgery.