Protein precipitation for the analysis of a drug cocktail in plasma by LC-ESI-MS

J Pharm Biomed Anal. 2004 Jun 29;35(4):913-20. doi: 10.1016/j.jpba.2004.03.005.


Three protein precipitation (PP) procedures with acetonitrile (ACN), perchloric acid (PA) and trichloroacetic acid (TCA) were investigated for the analysis of a drug cocktail from human plasma samples containing three pharmaceutical compounds and their primary metabolites. For this purpose, a capillary liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) method was developed for the simultaneous analysis of the six tested compounds in less than 6 min. Matrix effect was tested for each PP procedure by means of a post-column infusion system. The three PP techniques were found effective in removing proteins from human plasma and were fully compatible with capillary LC-ESI-MS analysis. However, with acid precipitations, low analyte recovery and a high variability, probably due to analyte coprecipitation, were obtained. Finally, ACN was found to be the most effective PP technique with a recovery higher than 80% and CV inferior to 6%.

MeSH terms

  • Blood Proteins / analysis*
  • Blood Proteins / metabolism
  • Chemical Precipitation
  • Chromatography, Liquid / methods
  • Humans
  • Spectrometry, Mass, Electrospray Ionization / methods*


  • Blood Proteins