Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation.
Anca Roxana PetroviciMihaela SilionNatalia SimionescuRami KallalaMariana PintealaStelian Sergiu MaierPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- ms ms
- high performance liquid chromatography
- mass spectrometry
- liquid chromatography
- tandem mass spectrometry
- simultaneous determination
- solid phase extraction
- gas chromatography
- liquid chromatography tandem mass spectrometry
- ultra high performance liquid chromatography
- high resolution mass spectrometry
- systematic review
- high resolution
- gas chromatography mass spectrometry
- air pollution
- quantum dots
- smoking cessation