title: Trimethylsilyldiazomethane derivatization coupled with solid-phase extraction for the determination of alendronate in human plasma by LC-MS/MS.
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.
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors: Meixia
authors: M
authors: Chen
authors: Ke
authors: K
authors: Liu
authors: Dafang
authors: D
authors: Zhong
authors: Xiaoyan
authors: X
authors: Chen
mesh_terms: D019386:Alendronate / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D003978:Diazomethane / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry; D014297:Trimethylsilyl Compounds / Q000737:chemistry*
chemical_list: D014297:Trimethylsilyl Compounds; D003978:Diazomethane; C060070:trimethylsilyldiazomethane; D019386:Alendronate