A LC-MS/MS method to quantify the novel cholesterol lowering drug ezetimibe in human serum, urine and feces in healthy subjects genotyped for SLCO1B1

J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Jan 2;830(1):143-50. doi: 10.1016/j.jchromb.2005.10.034. Epub 2005 Nov 8.


Ezetimibe (Ezetrol) is a novel cholesterol lowering drug which disposition is not fully understood in man. We developed a selective and high-sensitive assay to measure serum concentration-time profiles, renal and fecal elimination of ezetimibe in pharmacokinetic studies. Ezetimibe glucuronide, the major metabolite of ezetimibe was determined by enzymatic degradation to the parent compound. Ezetimibe was measured after extraction with methyl tert-butyl ether using 4-hydroxychalcone as internal standard and liquid chromatography coupled via an APCI interface with tandem mass spectrometry (LC-MS/MS) for detection. The chromatography (column XTerra) MS, C(18), 2.1 mm x 100 mm, particle size 3.5 microm) was done isocratically with acetonitrile/water (60/40, v/v; flow rate 200 microl/min). The MS/MS analysis was performed in the negative ion mode (m/z transition: ezetimibe 408-271, internal standard 223-117). The validation ranges for ezetimibe and total ezetimibe were as follows: serum 0.0001-0.015 microg/ml and 0.001-0.2 microg/ml; urine and fecal homogenate 0.025-10 microg/ml and 0.1-20 mg/ml, respectively. The assay was successfully applied to measure ezetimibe disposition in two subjects genotyped for the hepatic uptake transporter SLCO1B1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Anticholesteremic Agents / blood
  • Anticholesteremic Agents / pharmacokinetics*
  • Anticholesteremic Agents / urine
  • Azetidines / blood
  • Azetidines / pharmacokinetics*
  • Azetidines / urine
  • Base Sequence
  • Chromatography, Liquid / methods*
  • DNA Primers
  • Ezetimibe
  • Feces / chemistry*
  • Genotype
  • Humans
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Mass Spectrometry / methods*
  • Organic Anion Transporters / genetics*
  • Reference Standards
  • Reference Values


  • Anticholesteremic Agents
  • Azetidines
  • DNA Primers
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Ezetimibe