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.

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 / A.F. Lo Faro, R. Giorgetti, F.P. Busardò, G. Lodi, V. Martini, A. Pispero, IRITI MARCELLO, E.M. Varoni. - In: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS. - ISSN 0731-7085. - 162(2019 Jan 05), pp. 286-290.

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

A.F. Lo Faro;G. Lodi;A. Pispero;IRITI MARCELLO;E.M. Varoni
2019

Abstract

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.
Bisphosphonates; Liquid chromatography; Mass spectrometry; Osteonecrosis; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Chromatography, High Pressure Liquid; Female; Humans; Jaw; Male; Middle Aged; Reproducibility of Results; Zoledronic Acid; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Analytical Chemistry; 3003; Drug Discovery3003 Pharmaceutical Science; Spectroscopy; Clinical Biochemistry
Settore MED/28 - Malattie Odontostomatologiche
Settore MED/43 - Medicina Legale
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/707742
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