Novel UHPLC-MS/MS method for the determination of rotigotine in the plasma of patients with Parkinson's disease

Biomed Chromatogr. 2017 Sep;31(9). doi: 10.1002/bmc.3944. Epub 2017 Feb 20.

Abstract

A novel ultra-high-pressure liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of the dopamine receptor agonist rotigotine in human plasma. Following liquid-liquid extraction with tert-butyl methyl ether from 500 μL plasma, the chromatographic analysis was performed on a Gemini NX3 column using 5 mm pH 5.0 ammonium acetate-5 mm ammonium acetate in methanol as binary gradient mobile phase, at a flow rate of 0.3 mL/min. The MS/MS ion transitions were 316.00 → 147.00 for rotigotine and 256.10 → 211.00 for the internal standard (lamotrigine). The lower limit of quantitation was 50 pg/mL and the linearity was determined from 50 to 2500 pg/mL. The mean recovery was 96.9%. Both intra- and interassay imprecision and inaccuracy were ≤15% at all quality control concentrations. The method was successfully applied to measure morning trough plasma rotigotine concentrations in a series of patients with Parkinson's disease on chronic treatment. The present study describes the first fully validated method for rotigotine determination in human plasma.

Keywords: Parkinson's disease; UHPLC-MS/MS; dopamine receptor agonist; rotigotine.

MeSH terms

  • Chromatography, High Pressure Liquid / methods*
  • Dopamine Agonists / blood*
  • Dopamine Agonists / chemistry
  • Dopamine Agonists / pharmacokinetics
  • Dopamine Agonists / therapeutic use
  • Humans
  • Limit of Detection
  • Linear Models
  • Parkinson Disease / drug therapy*
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*
  • Tetrahydronaphthalenes / blood*
  • Tetrahydronaphthalenes / chemistry
  • Tetrahydronaphthalenes / pharmacokinetics
  • Tetrahydronaphthalenes / therapeutic use
  • Thiophenes / blood*
  • Thiophenes / chemistry
  • Thiophenes / pharmacokinetics
  • Thiophenes / therapeutic use

Substances

  • Dopamine Agonists
  • Tetrahydronaphthalenes
  • Thiophenes
  • rotigotine