Simultaneous quantitation of levodopa and 3-O-methyldopa in human plasma by HPLC-ESI-MS/MS: application for a pharmacokinetic study with a levodopa/benserazide formulation

J Pharm Biomed Anal. 2011 Dec 15;56(5):1094-100. doi: 10.1016/j.jpba.2011.07.040. Epub 2011 Jul 30.

Abstract

A sensitive and simple method was developed for the quantitation of levodopa and its metabolite 3-O-methyldopa, in human plasma, after oral administration of tablet formulations containing levodopa (200 mg) and benserazide (50 mg). The analytes were extracted by a protein precipitation procedure, using carbidopa as an internal standard. A mobile phase consisting of 0.2% formic acid and acetonitrile (94:6, v/v) was used and chromatographic separation was achieved using ACE C(18) column (50 mm×4.6 mm i.d.; 5 μm particle size). Selected reaction monitoring was performed using the fragmentation transitions m/z 198→m/z 107, m/z 212→m/z 166 and m/z 227→m/z 181 for levodopa, 3-O-methyldopa and carbidopa, respectively. Calibration curves were constructed over the range 50.0-6000.0 ng/mL for levodopa and 25.0-4000.0 ng/mL for 3-O-methyldopa. The method shown to be specific, precise, accurate and provided recovery rates higher than 85% for all analytes. No matrix effect was detected in the samples. The validated method was applied in a pharmacokinetic study with a levodopa/benserazide tablet formulation in healthy volunteers.

Publication types

  • Validation Study

MeSH terms

  • Benserazide / blood*
  • Benserazide / pharmacokinetics
  • Calibration
  • Chromatography, High Pressure Liquid / methods*
  • Humans
  • Levodopa / blood*
  • Levodopa / pharmacokinetics
  • Methyldopa / blood*
  • Methyldopa / pharmacokinetics
  • Quality Control
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Tablets
  • Tandem Mass Spectrometry / methods*

Substances

  • Tablets
  • Levodopa
  • Methyldopa
  • Benserazide