title: 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.
abstract: 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.
  
  
  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.
  
  
  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.
authors.forename: Shu-Qiao
authors.initials: SQ
authors.lastname: Cheng
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Ouyang
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Tang
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005283:Fentanyl / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D059625:Liquid-Liquid Extraction; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
chemical_list: D005283:Fentanyl