Development and validation of a method using ultra performance liquid chromatography coupled to tandem mass spectrometry for determination of zoledronic acid concentration in human bone

• Published in: Journal of pharmaceutical and biomedical analysis 2019-01, Vol.162, p.286-290
• Main Authors: Lo Faro, Alfredo Fabrizio, Giorgetti, Raffaele, Busardò, Francesco Paolo, Lodi, Giovanni, Martini, Valeria, Pispero, Alberto, Iriti, Marcello, Varoni, Elena Maria
• Format: Article
• Language: English
• Subjects: Bisphosphonate-Associated Osteonecrosis of the Jaw - diagnosis; Bisphosphonate-Associated Osteonecrosis of the Jaw - etiology; Bisphosphonate-Associated Osteonecrosis of the Jaw - metabolism; Bisphosphonate-Associated Osteonecrosis of the Jaw - surgery; Bisphosphonates; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - metabolism; Chromatography, High Pressure Liquid - methods; Female; Humans; Jaw - drug effects; Jaw - metabolism; Liquid chromatography; Male; Mass spectrometry; Middle Aged; Osteonecrosis; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Zoledronic Acid - adverse effects; Zoledronic Acid - metabolism
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2018.09.042

•Bisphosphonates are widely used for the treatment of osteoporosis and bone malignancies.•Zoledronic acid, a commonly prescribed bisphosphonate, strongly binds bone tissue and inhibits osteoclast function.•A method for the extraction and quantification of zoledronic acid from human bone was set up and validated.•Quantificazion of zoledronic acid from jawbone was obtained in patients with osteonecrosis. A method for the extraction and quantification of zoledronic acid (ZA) from human bone was set up and validated. This method allowed the quantification of ZA from jawbone sequestrations of patients affected by bisphosphonate-related osteonecrosis of the jaw (BRONJ) associated with ZA treatment. The analyte was extracted from the bone tissues with phosphoric acid and derivatized using trimethylsilyl diazomethane (TMS-DAM). ZA tetramethyl phosphonate was then quantified by liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS), showing high accuracy, repeatability and selectivity. Lower limits of quantification and detection (LLOQ and LLQD) were 3.4 ng/mL and 1 ng/mg, respectively. This study fully described the analytical process for the determination of ZA in human bone sequestrations, representing a pivotal step for further biomedical research on ZA and BRONJ.