A rapid, simple and sensitive method for the determination and bioequivalence study of transdermal fentanyl in human plasma using liquid chromatography-electrospray ionization tandem mass spectrometry.

Objective: Since the 1960s, fentanyl has been used to replace morphine nd other opioids due to its higher potency in the treatment of acute pain; since the 1990s, it has also been administrated to control chronic pain by using transdermal fentanyl device system. It is crucial and of utmost importance and crucial to validate a sensitive method for the quantification of transdermal fentanyl in human plasma.

Materials And Methods: A rapid, simple and sensitive high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method has been established and validated for the determination of transdermal fentanyl in human plasma using fentanyl-D5 as an internal standard (IS). Following liquid-liquid extraction (LLE) with n-hexane, the extracts were separated on a Thermo Hypersil ODS(C18) column (2.1 × 150 mm i.d., 5 μm) interfaced with a triple-quadrupole tandem mass spectrometer using positive electrospray ionization.

Results And Conclusions: Quantification of fentanyl was carried out by multiple reaction monitoring (MRM) of the transitions at m/z 337.1→188.0 for fentanyl and 341.9→187.9 for IS. The lower limit of quantification was 9.75 pg×mL-1, and the test showed a linear range of 9.75 - 10,000 pg×mL-1. The validated method was subsequently applied to a bioequivalence (BE) study in 24 healthy Chinese volunteers by using transdermal fentanyl patches.