A sensitive and accurate liquid chromatography-tandem mass spectrometry method for quantitative determination of the novel hepatitis C NS5A inhibitor BMS-790052 (daclastasvir) in human plasma and urine

J Chromatogr A. 2012 Jul 6:1245:117-21. doi: 10.1016/j.chroma.2012.05.028. Epub 2012 May 14.

Abstract

A liquid-liquid extraction (LLE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed and validated for the quantification of BMS-790052 (daclastasvir) in human plasma and urine. The samples were extracted with methyl-t-butyl ether (MTBE) before analyzing by an API 4000 mass spectrometer which was operated in a multiple reaction monitoring (MRM) mode for detection of positively charged ions of BMS-790052 and its internal standard, ¹³C₁₀-BMS-790052. The standard curves ranged from 0.050 to 50.0 ng/mL for BMS-790052 in human plasma, and 1.00-1000 ng/mL in human urine. The intra-assay precision (%CV), based on four levels of analytical QCs (low, geometric mean, mid and high), was within 8.6%; inter-assay precision (%CV) was within 6.7% for both plasma and urine methods, and the mean assay accuracy (%Dev) was within ±3.0% for both plasma and urine methods. The ruggedness of this accurate, precise, and selective LLE-LC-MS/MS method has been demonstrated in the successful analysis of several thousand clinical study samples.

Publication types

  • Evaluation Study

MeSH terms

  • Carbamates
  • Chromatography, Liquid / methods*
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / metabolism
  • Hepatitis C / blood*
  • Hepatitis C / urine*
  • Humans
  • Imidazoles / blood*
  • Imidazoles / isolation & purification
  • Imidazoles / urine*
  • Liquid-Liquid Extraction
  • Pyrrolidines
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*
  • Valine / analogs & derivatives
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Carbamates
  • Imidazoles
  • Pyrrolidines
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus
  • Valine
  • daclatasvir