Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation
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...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/5944 |
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| author | Anca-Roxana Petrovici Mihaela Silion Natalia Simionescu Rami Kallala Mariana Pinteala Stelian S. Maier |
| author_facet | Anca-Roxana Petrovici Mihaela Silion Natalia Simionescu Rami Kallala Mariana Pinteala Stelian S. Maier |
| author_sort | Anca-Roxana Petrovici |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T01:17:09Z |
| format | Article |
| id | doaj.art-75f836bbc1ee47fcbf9a43a2fb1e3f38 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:17:09Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-75f836bbc1ee47fcbf9a43a2fb1e3f382023-11-23T14:06:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012311594410.3390/ijms23115944Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and ValidationAnca-Roxana Petrovici0Mihaela Silion1Natalia Simionescu2Rami Kallala3Mariana Pinteala4Stelian S. Maier5Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487 Iasi, RomaniaPhysics of Polymers and Polymeric Materials Department, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487 Iasi, RomaniaCentre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487 Iasi, RomaniaCorthotec Limited, 130 Wood Street, London EC2V 6DL, UKCentre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487 Iasi, RomaniaCentre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487 Iasi, RomaniaZoledronic 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.https://www.mdpi.com/1422-0067/23/11/5944zoledronic acid (ZA)calcium sulfate hemihydratesolid inorganic matrixHPLC-ESI-MS analysisextracted ion chromatogram (EIC)ZA-calcium complexes |
| spellingShingle | Anca-Roxana Petrovici Mihaela Silion Natalia Simionescu Rami Kallala Mariana Pinteala Stelian S. Maier Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation International Journal of Molecular Sciences zoledronic acid (ZA) calcium sulfate hemihydrate solid inorganic matrix HPLC-ESI-MS analysis extracted ion chromatogram (EIC) ZA-calcium complexes |
| title | Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation |
| title_full | Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation |
| title_fullStr | Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation |
| title_full_unstemmed | Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation |
| title_short | Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation |
| title_sort | quantification of low amounts of zoledronic acid by hplc esi ms analysis method development and validation |
| topic | zoledronic acid (ZA) calcium sulfate hemihydrate solid inorganic matrix HPLC-ESI-MS analysis extracted ion chromatogram (EIC) ZA-calcium complexes |
| url | https://www.mdpi.com/1422-0067/23/11/5944 |
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