Arnaud Capron1, Jennifer Destree2, Dominique Maiter3, Pierre Wallemacq4. 1. Clinical Chemistry Department, Cliniques Universitaires St Luc, Brussels, Belgium; Louvain Center for Toxicology and Applied Pharmacology, Université Catholique de Louvain, UCL, Brussels, Belgium. 2. Clinical Chemistry Department, Cliniques Universitaires St Luc, Brussels, Belgium. 3. Department of Endocrinology and Nutrition, Cliniques Universitaires St Luc, Brussels, Belgium. 4. 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.
Abstract
OBJECTIVES: 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. DESIGN AND 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. CONCLUSION: 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.
OBJECTIVES: 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. DESIGN AND 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. CONCLUSION: 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.