title: Validation of a rapid liquid chromatography-tandem mass spectrometric assay for the determination of octreotide plasma concentrations.
abstract: OBJECTIVE
  The aim of this study was to develop and validate a fast liquid chromatography-tandem mass spectrometric (LC-MSMS) assay to determine circulating concentrations of octreotide (a somatostatin analog used in acromegaly and neuroendocrine tumors) in patients' plasma samples.
  
  
  METHODS
  500 μL of heparin-plasma was used to extract the drug on a cation exchanger SPE column, and the eluate was injected into a LC-MSMS system. Reversed phase chromatography was performed on a phenyl grafted column in isocratic mode. Octreotide and internal standard (triptorelin) were identified in positive electrospray ionization mode using ion transitions of m/z 512>120 and 890>249, respectively.
  
  
  RESULTS
  The assay was linear in the concentration range of 0.5-25 ng/mL, with intra- and inter-assay imprecisions of <10.6% and <12.2%, respectively. The limits of quantification and detection were 0.5 and 0.25 ng/mL. The recovery and ion suppression effect ranged between 79.7 and 84.5% and between -8.1 and -21.3%, respectively. A subcutaneous injection of 0.1mg octreotide induced a time- and patient-dependent surge of peptide concentrations peaking at 2h.
  
  
  CONCLUSIONS
  This fast, sensitive, and selective method for quantification of plasma octreotide by LC-MSMS might be used to investigate the pharmacokinetic-pharmacodynamic relationship, with potential contribution to treatment optimization and therapeutic drug monitoring application.
authors.affiliation: Clinical Chemistry Department, Cliniques Universitaires St Luc, Brussels, Belgium; Louvain Center for Toxicology and Applied Pharmacology, Université Catholique de Louvain, UCL, Brussels, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Capron
authors.affiliation: Clinical Chemistry Department, Cliniques Universitaires St Luc, Brussels, Belgium.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Destree
authors.affiliation: Department of Endocrinology and Nutrition, Cliniques Universitaires St Luc, Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Maiter
authors.affiliation: Clinical Chemistry Department, Cliniques Universitaires St Luc, Brussels, Belgium; Louvain Center for Toxicology and Applied Pharmacology, Université Catholique de Louvain, UCL, Brussels, Belgium. Electronic address: pierre.wallemacq@uclouvain.be.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wallemacq
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D015282:Octreotide / Q000097:blood*; D012015:Reference Standards; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015282:Octreotide
keywords: Acromegaly; Liquid-chromatography mass-spectrometry; Octreotide; Therapeutic drug monitoring