Impurity profile study of zaleplon

J Pharm Biomed Anal. 2007 May 9;44(1):101-9. doi: 10.1016/j.jpba.2007.01.051. Epub 2007 Feb 6.

Abstract

Zaleplon is a pyrazolopyrimidine derivative and possesses sedative and hypnotic properties. Seven unknown impurities in zaleplon bulk drug at levels below 0.1% were detected by reverse-phase high performance liquid chromatography (HPLC). The starting material, 3-amino-4-cyanopyrazole and an intermediate, N-[3-[3-(dimethylamino)-1-oxo-2-propenyl]-phenyl]-N-ethylacetamide (DOPEA) were also present in the sample at a level below 0.1%. The molecular weights of impurities were determined by LC-MS analysis. These impurities were isolated from crude samples of zaleplon using reverse-phase preparative HPLC. Based on the spectral data the structures of these impurities were characterized as, N-(3-(3-(4-amino-2H-pyrazolo [3,4-d]pyrimidin-6-yl) pyrazolo[1,5-a] pyrimidin-7-yl)phenyl)-N-ethylacetamide (impurity I); N-[3-(3-carboxamidopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide (impurity II); N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]acetamide (impurity III); N-[3-(3-cyanopyrazolo [1,5-a]pyrimidin-7-yl)phenyl]-N-methylacetamide (impurity IV); N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-5-yl)phenyl]-N-ethylacetamide (impurity V); N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl]-N-ethylamine (impurity VI); N-[3-(3-cyano-6-[(E)-3-((N-ethyl-N-acetyl)amino)phenyl-3-oxoprop-1-enyl] pyrazolo[1,5-a]pyrimidin-7-yl) phenyl]-N-ethylacetamide (impurity VII). Structural elucidation of all impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and formation of these impurities are discussed in detail.

MeSH terms

  • Acetamides / analysis*
  • Acetamides / chemical synthesis
  • Acetamides / chemistry
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Drug Contamination*
  • Hypnotics and Sedatives / analysis*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Molecular Weight
  • Pyrimidines / analysis*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Transition Temperature

Substances

  • Acetamides
  • Hypnotics and Sedatives
  • Pyrimidines
  • zaleplon