Alternative strategies for mass spectrometer-based sample dilution of bioanalytical samples, with particular reference to DBS and plasma analysis.

Background: The analysis of bioanalytical samples has required a physical dilution of high-concentration samples to bring concentrations into the validated calibration range of an assay.

Results: A reversed phase ultra-high performance liquid chromatography-tandem mass spectrometry method for the quantitative analysis of pioglitazone in dried blood spots has been used to partially validate two novel techniques to analyze sample concentrations that lie above a particular calibration range. The first of the two techniques is mass spectrometer signal dilution, which consists of lowering the signal that reaches the detector.

Validation of a bioanalytical method for the quantification of a therapeutic peptide, ramoplanin, in human dried blood spots using LC-MS/MS.

A method has been developed and validated for the quantification of ramoplanin, a 2554 Da peptide antibiotic, in human dried blood spots using high-performance liquid chromatography with tandem mass spectrometric detection. The validation data meet FDA acceptance criteria for bioanalytical assays and cover the quantification of ramoplanin over the range 10-5000 ng/mL. The assay determines ramoplanin at the same lower limit of quantification as conventional liquid sample methods.

Application of the DBS methodology to a toxicokinetic study in rats and transferability of analysis between bioanalytical laboratories.

Background: There are little published data on either the comparison of liquid blood and dried blood spots (DBS) analyses or the ability to generate comparable DBS data at different analytical laboratories. We assess the comparative results of samples stored as liquid blood and DBS. We also determine the transferability of DBS samples by comparing the analysis at two laboratories.