title: Quantitative analysis of bisphosphonates in biological samples.
abstract: Bisphosphonate drugs pose significant challenges for bioanalysis due to various complicating factors. In 2006, a novel approach, utilizing 'on-column' derivatization with diazomethane, was reported that revolutionized the application of liquid-chromatography-tandem mass spectrometry to bisphosphonates bioanalysis. The methodology enables superior biological sample clean-up while transforming bisphosphonates into species amenable to liquid-chromatography-tandem mass spectrometry detection. Since then, the approach has been successfully applied to numerous bisphosphonates. The use of an alternative methylation reagent - trimethylsilyl diazomethane - for on-column derivatization has been reported recently. This review focuses on published methods utilizing on-column derivatization for bioanalysis of major bisphosphonate drugs in biological matrices. Critical points required for successful application of on-column derivatization to the bioanalysis of bisphosphonates will be discussed.
authors.affiliation: Celerion, 621 Rose Street, Lincoln, NE USA 68502.
authors.forename: Veniamin N
authors.initials: VN
authors.lastname: Lapko
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Miller
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Sheldon
authors.forename: Ridha
authors.initials: R
authors.lastname: Nachi
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Kafonek
mesh_terms: D050071:Bone Density Conservation Agents / Q000032:analysis* / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004164:Diphosphonates / Q000032:analysis* / Q000097:blood / Q000652:urine; D006801:Humans; D057230:Limit of Detection; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates