title: [Determination of dextrorphan in human plasma and pharmacokinetic study].
abstract: OBJECTIVE
  To develop a sensitive and specific LC/MS/MS method for direct determination of dextrorphan in human plasma and to study the pharmacokinetics of dextrorphan.
  
  
  METHODS
  After a single oral dose of 60 mg dextromethorphan hydrobromide to 18 healthy Chinese male volunteers, the plasma concentration of dextrorphan, an active metabolite of dextromethorphan, was determined. Dextrorphan and internal standard chlorpheniramine were extracted from plasma using liquid-liquid extraction, then separated on a Zorbax Extend C18 column. The mobile phase consisted of methanol-water-formic acid (70:30:1), at a flow-rate of 0.5 mL x min(-1). A Finnigan TSQ tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor to product ion combinations of m/z 258 to 157 and m/z 275 to 230 was performed to quantify dextrorphan. The pharmacokinetic parameters of dextrorphan were calculated by non-compartment model statistics.
  
  
  RESULTS
  The linear calibration curves were obtained in the concentration range of 0.2 - 80 microg x L(-1) Each plasma sample was chromatographed within 3.0 min. The intra- and inter-day relative standard deviation (RSD) across three validation runs over the entire concentration range was less than 8%. Accuracy determined at three concentrations (0.5, 6.0 and 70 microg x L(-1) for dextrorphan) ranged from 98.8% to 100.6%. Pharmacokinetic parameters of dextrorphan was obtained as follows: Tmax was (2.1 +/- 0.7) h, Cmax was (14 +/- 8) microg x L(-1), T1/2 was (3.8 +/- 1.8) h, AUC0-t was (60 +/- 37) microg x h x L(-1).
  
  
  CONCLUSIONS
  Plasma concentration of the active metablite dextrorphan was directly determined. The method is sensitive and convenient, and is proved to be suitable for clinical investigation of dextrorphan pharmacokinetics and bioequivalence evaluation of formulations containing dextromethorphan.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Yi-fan
authors.initials: YF
authors.lastname: Zhang
authors.forename: Da-fang
authors.initials: DF
authors.lastname: Zhong
authors.forename: Qi
authors.initials: Q
authors.lastname: Gu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D003915:Dextromethorphan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003917:Dextrorphan / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization; D013810:Therapeutic Equivalency
chemical_list: D003917:Dextrorphan; D003915:Dextromethorphan