期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/ijms23115944
关键词
zoledronic acid (ZA); calcium sulfate hemihydrate; solid inorganic matrix; HPLC-ESI-MS analysis; extracted ion chromatogram (EIC); ZA-calcium complexes; method development and validation
资金
- Ministry of Research and Innovation, CNCS-UEFISCDI, within PNCDI III [PN-III-P4-ID-PCCF-2016-0050]
- European Social Fund for Regional Development, Competitiveness Operational Programme Axis 1, Action: 1.1.3, Project Infra SupraChem LabCenter for Advanced Research in Supramolecular Chemistry [339/390015, 108983]
This study describes the identification of ZA-calcium complexes in calcium-rich environments and proposes a new method for quantification of low ZA amounts. The method avoids compound derivatization and utilizes high-performance liquid chromatography and electrospray ionization mass spectrometry. It can accurately quantify low concentrations of ZA in the blood.
Zoledronic acid (ZA) is used in the treatment of various bone pathologies, but it forms complexes with calcium ions present in body fluids, decreasing ZA bioavailability. Thereby, the study first describes the identification of ZA-calcium complexes that form in calcium-rich environments, in order to establish the bioavailable ZA concentration. Then, a new method for quantification of low ZA amounts in milieus that mimics in vivo conditions by using simulated body fluid and calcium sulfate hemihydrate was described. Almost all analytical methods of ZA quantification described in the literature require compound derivatization. At very low concentrations, derivatization is prone to analyte loss, therefore compromising the analytical results. In our study, we avoided ZA derivatization by using a high-performance liquid chromatography and electrospray ionization mass spectrometry (HPLC-ESI-MS) system, conducting the investigation based on the fragmentation mass extracted ion chromatograms specific to the ZA protonated form. The method was validated by selectivity, precision, accuracy, linearity, signal to noise ratio, and limit of detection and limit of quantification calculation. Experimentally, this method can detect ranges of 0.1-0.5 ng/mL and precisely quantify ZA concentrations as low as 0.1 ng/mL. This method could provide the basis for quantifying low amounts of ZA in the blood during long-term administration.
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