Quantitative analysis of bisphosphonates in biological samples.

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.

Sensitive glucagon quantification by immunochemical and LC-MS/MS methods.

The peptide hormone glucagon plays an important role in homeostasis of glucose concentrations in the blood. Its biological importance is evidenced through the conservation of its peptide sequence between species. Reliable assays for glucagon in biological samples are important for gaining a better understanding of the pathology and treatment of diabetes. Numerous assays are available for the analysis of glucagon in biological samples, the majority of which employ an immunochemical approach and have been available for many years. However, recent advances in MS instrumentation and the amenability of glucagon for analysis by LC-MS/MS has brought these new methods to the forefront. Concentrations of glucagon determined from different methods are not always consistent and this review provides suggestions of how to improve the reliability of methods for glucagon analysis.