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Trimethylsilyldiazomethane derivatization coupled with solid-phase extraction for the determination of alendronate in human plasma by LC-MS/MS

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Abstract

Alendronate is an important representative of bisphosphonates, strongly polar compounds that lack chromophores. With rare exceptions, derivatization of the analytes is necessary for bioanalysis. In this study, a rapid liquid chromatography–tandem mass spectrometry method employing pre-column derivatization was developed and validated for the determination of alendronate concentrations in human plasma. The procedure was based on derivatization with trimethylsilyldiazomethane during solid-phase extraction on a weak anion-exchange solid-phase cartridge, which integrated sample purification and derivatization into one step. The alendronate derivative was eluted with methanol. Chromatographic separation was performed on a Capcell PAK-C18 column. The total run time was 6.5 min. The calibration curve was linear in the range 1.00–1,000 ng/mL using d6-alendronate as the internal standard. The lower limit of quantification was 1.00 ng/mL. The intra- and inter-assay precision (in RSD) calculated from quality control samples was less than 15%, and the accuracy was between 98.1% and 100.2%. The validated method was successfully applied to characterize the pharmacokinetic profiles of alendronate following the intravenous infusion of 5 or 10 mg alendronate sodium to healthy volunteers.

Derivatization and determination procedures of alendronate in human plasma

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Acknowledgment

This study was partly supported by the National Basic Research Program of China (2009CB930300).

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Authors and Affiliations

  1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China

    Meixia Chen, Ke Liu, Dafang Zhong & Xiaoyan Chen

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  1. Meixia Chen
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  2. Ke Liu
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  3. Dafang Zhong
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  4. Xiaoyan Chen
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Correspondence to Xiaoyan Chen.

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Chen, M., Liu, K., Zhong, D. et al. Trimethylsilyldiazomethane derivatization coupled with solid-phase extraction for the determination of alendronate in human plasma by LC-MS/MS. Anal Bioanal Chem 402, 791–798 (2012). https://doi.org/10.1007/s00216-011-5467-4

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  • DOI: https://doi.org/10.1007/s00216-011-5467-4

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