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. The second technique designated isotope signal ratio monitoring looks at [M+2]+1 ions (caused by naturally occurring isotopes) for samples above the upper limit of quantification.


CONCLUSIONS
The newly developed methods have the potential to simplify the analysis of bioanalytical samples for which previously a physical dilution of the sample was required to bring analytes within the calibration range of an assay.
Covance Laboratories Ltd, Otley Road, Harrogate, North Yorkshire, HG3 1PY, UK.
Ranbir S
RS
Mannu
Phillip E
PE
Turpin
Lee
L
Goodwin
D001681:Biological Assay / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D059788:Dried Blood Spot Testing; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods