A thorough LC-MS/MS strategy to quantify abaloparatide in rat plasma: method development, validation and application

BACKGROUND: Abaloparatide is a newly approved analog of parathyroid hormone-related peptide. It is used for the treatment of osteoporosis in postmenopausal women who have a high risk of fracture. The aim of our work was to establish a novel liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method to achieve rapid, sensitive and robust quantification of abaloparatide in biological samples. RESULTS: and was further demonstrated to be accurate and precise. Meanwhile, the method presented acceptable recoveries for abaloparatide (88.7-103%) and the internal standard (102%), and there was no significant matrix effect. Abaloparatide was proved to be stable under the conditions of 4 °C for 2 h at -80 °C for 50 days and three freeze-thaw cycles (-80 °C to 4 °C). The method was successfully applied to the pharmacokinetic study of abaloparatide in rats after subcutaneous administration. SIGNIFICANCE: To the best of our knowledge, this is the first mass spectrometry-based method developed to quantify abaloparatide in plasma samples. It not only offers an attractive choice for abaloparatide development but may also promote the application of LC-MS/MS in peptide bioanalysis.