Development and validation of an LC-MS/MS method for the quantification of goserelin in a Pheroid® formulation, in simulated intestinal fluid

J Pharm Biomed Anal. 2020 Feb 20:180:113044. doi: 10.1016/j.jpba.2019.113044. Epub 2019 Dec 12.

Abstract

The purpose of this reported study was to develop and validate an LC-MS/MS method for the quantification of goserelin in a Pheroid® formulation simulated intestinal fluid. Biopharmaceuticals are formulated in drug delivery systems to improve their gastrointestinal stability. Goserelin, a peptide drug was formulated in Pheroid® delivery system and its gastrointestinal stability assessed using simulated intestinal fluid, which required an assay to determine the varying amounts of goserelin remaining after a specific time. Several extraction methods and solvents investigated to extract goserelin from complex matrix led to either poor recovery, peak shape or high background interference. A rapid gradient reversed-phase method coupled to tandem mass spectrometry detection was optimized for the separation and quantification of the extracted peptide. A simple, reproducible and good recovery extraction procedure for goserelin quantification was achieved through simultaneous acetonitrile protein precipitation and water-saturated n-butanol liquid-liquid extraction with water dilution. The method was found to be rapid, specific, precise and accurate, and successfully applied to determine goserelin remaining content in a simulated intestinal fluid, with potential use in other lipid-based formulation evaluated in simulated intestinal fluids.

Keywords: Goserelin; LC-MS/MS; Method validation; Peptide; Pheroid® formulation; Simulated intestinal fluid.

MeSH terms

  • Biomimetic Materials / metabolism*
  • Biosensing Techniques
  • Chromatography, High Pressure Liquid
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Drug Liberation
  • Extracellular Fluid / metabolism*
  • Goserelin / chemistry*
  • Goserelin / pharmacology*
  • Limit of Detection
  • Linear Models
  • Liquid-Liquid Extraction
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Solvents / chemistry
  • Tandem Mass Spectrometry / methods*

Substances

  • Drug Carriers
  • Solvents
  • Goserelin