Simultaneous determination of N-ethylpentylone, dopamine, 5-hydroxytryptamine and their metabolites in rat brain microdialysis by liquid chromatography tandem mass spectrometry

Biomed Chromatogr. 2019 Oct;33(10):e4626. doi: 10.1002/bmc.4626. Epub 2019 Jul 18.

Abstract

N-Ethylpentylone (NEP) is a popular synthetic cathinone abused worldwide. To obtain more information about its pharmacokinetics and pharmacodynamics, a rapid, simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the determination of NEP, two important neurotransmitters, dopamine and serotonin, and their metabolites, including 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and 5-hydroxyindole-3-acetic acid, in rat brain microdialysate. The analytes were separated on a Phnomenex Polar C18 column, with a mobile phase of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) under gradient elution to shorten the total chromatographic run time. A triple quadruple mass spectrometer coupled with an electrospray ionization source in both positive and negative ion mode was used to detect the analytes. This method showed excellent accuracy (87.4-113.5%) and precision (relative standard deviation <15%) at three quality control levels. The limits of detection were 0.2 ng/mL for NEP and 0.2-50 nm for the others and good linearity was obtained. This study pioneered a method to integrate exogenous drugs and endogenous neurotransmitters as the drugs act on the same determination system, which means that this innovation can provide support for further study of the addictive effects of NEP or other synthetic cathinones on extracellular levels of dopamine and 5-hydroxytryptamine.

Keywords: 5-hydroxytryptamine; LC-MS/MS; N-ethylpentylone; dopamine; psychostimulants.

MeSH terms

  • Animals
  • Benzodioxoles / administration & dosage
  • Benzodioxoles / analysis*
  • Benzodioxoles / pharmacokinetics
  • Butylamines / administration & dosage
  • Butylamines / analysis*
  • Butylamines / pharmacokinetics
  • Chromatography, High Pressure Liquid / methods*
  • Dopamine / analysis*
  • Dopamine / metabolism
  • Limit of Detection
  • Linear Models
  • Microdialysis
  • Nucleus Accumbens / chemistry*
  • Nucleus Accumbens / metabolism
  • Rats
  • Reproducibility of Results
  • Serotonin / analysis*
  • Serotonin / metabolism
  • Tandem Mass Spectrometry / methods

Substances

  • Benzodioxoles
  • Butylamines
  • N-ethylpentylone
  • Serotonin
  • Dopamine