Quantitative determination of sufentanil in human plasma by liquid chromatography-tandem mass spectrometry

A sensitive and specific method for the quantification of sufentanil in human plasma by liquid chromatography coupled with tandem mass spectrometry has been developed. Fentanyl was used as the internal standard. Rapid sample preparation involved purification on a C(18) solid-phase extraction column. Chromatographic separation of the analytes was obtained using an RP-C(18) mu-HPLC column. LC-MS-MS detection was performed by atmospheric pressure ionisation (API) source equipped with an ionspray (IS) interface operating in the positive ion mode. For unambiguous substance confirmation, three analyte precursor-product ion combinations were monitored during multiple reaction monitoring (MRM) LC-MS-MS analysis. The method's performance characteristics were evaluated in blank and spiked control plasma samples. Overall accuracy (relative error, R.E., %), repeatability (relative standard deviations, R.S.D., %) and within-laboratory reproducibility (R.S.D., %) ranged from -9.28 to -2.71%, from 6.42 to 2.82% and from 13.52 to 6.06%, respectively, for sufentanil. The limit of quantification for sufentanil in human plasma samples was 0.3 ng ml(-1). Due to its high sensitivity and specificity, the method was successfully employed for sufentanil determination in maternal plasma samples collected immediately before epidural administration of a single sufentanil dose to women in labour, 20 min after drug administration, and at birth in arterial and venous umbilical cord plasma samples from the newborn babies. Research is in progress to adopt the method for performance of complete pharmacokinetic studies of sufentanil in human plasma.