A simple, effective approach for rapid development of high-throughput and reliable LC-MS/MS bioanalytical assays

Bioanalysis. 2016 Sep;8(17):1809-22. doi: 10.4155/bio-2016-0100. Epub 2016 Aug 5.

Abstract

Background: Rapidly developing LC-MS/MS assays with high-throughput and quality are challenging yet desired. Methodology & results: A simple method development approach was reported and demonstrated with the quantitative bioanalysis of BMS-984478, a hepatitis C virus nonstructural protein 5A inhibitor. An accurate, precise and robust LC-MS/MS method for the quantitation of BMS-984478 in rat and monkey plasma was developed and validated. Incurred sample reanalysis evaluation passed with 100% of samples meeting the acceptance criteria. The validated assay was successfully applied in toxicology studies without any failed runs.

Conclusion: The approach was successfully applied to the bioanalysis of BMS-984478 in toxicology and clinical studies. This approach was shown to be effective and reliable in speeding the development of high-throughput and reliable LC-MS/MS assays.

Keywords: UHPLC–MS/MS; incurred sample; matrix effect; metabolite interference; method development; regulated bioanalysis.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Antiviral Agents / blood*
  • Antiviral Agents / toxicity
  • Chromatography, High Pressure Liquid / economics
  • Chromatography, High Pressure Liquid / methods
  • Haplorhini
  • Hepacivirus / drug effects
  • Hepatitis C / drug therapy
  • Humans
  • Limit of Detection
  • Rats
  • Reproducibility of Results
  • Tandem Mass Spectrometry / economics
  • Tandem Mass Spectrometry / methods*
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus