Quantitative Determination of Cinacalcet in Dialysis Patients' Plasma by a High Performance Liquid Chromatography Mass Spectrometry Method / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish a high performance liquid chromatography mass spectrometry (HPLC-MS/MS) method to determine the cinacalcet concentration in plasma of dialysis patients. METHODS: Fendiline hydrochloride was selected as the internal standard (IS), in the meantime, plasma samples were extracted through the solid phase extraction (SPE), and the internal standard method was used to determine the concentration of cinacalcet. The analyte was separated by Inertsil SIL-150A (2.1 mm×50 mm, 5 μm) matched with guard column Inertsil SIL-150A (3.0 mm×50 mm,5 μm). The cinacalcet was eluted with acetonitrile, water and formic acid (90101=VVV) at a rate of 0.35 mL•min-1. On MS, electrospray ionization (ESI) source with positive ion mode and multiply reaction monitoring (MRM) was used. The MRM transitions of cinacalcet and the IS were 358.1→155.1 and 316.0→212.1, respectively. The concentration in dialysis patients after 25 mg dose (one piece of tablet) within 24 h was determined by using the established HPLC-MS/MS method in this paper. RESULTS: A good linearity was obtained in the range of 0.1-50 ng•mL-1 of cinacalcet, and the validated accuracy and precision all were within ±15%. Long-term, freeze-thaw and autoinjector stability of cinacalcet QC samples were all in the range of 1.4%-3.9%. The matrix of cinacalcet is (104.5±3.1)%, (105.6±4.3)% and (104.0±3.1)% respectively and the matrix of IS is (106.4±3.0)%. This validated method can meet the guidance for bioanalytical method validation. CONCLUSION: The HPLC-MS/MS method is sensitive and specific enough to meet the quantitative requirements for determining cinacalcet in human plasma. It is rapid, accurate and in line with the guidance for bioanalytical method validation.