Validation of a rapid liquid chromatography-tandem mass spectrometric assay for the determination of octreotide plasma concentrations

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 0.1 mg octreotide induced a time- and patient-dependent surge of peptide concentrations peaking at 2 h. 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. © 2013 The Canadian Society of Clinical Chemists.