Validation of new instrumentation for isotope dilution mass spectrometric determination of organic serum analytes

A major activity in the 20 year collaboration between the Analytical Chemis try Division at NIST and the College of American Pathologists (CAP) has bee n the development of highly accurate and precise "definitive" methods for i mportant clinical analytes in human serum. Definitive methods for organic a nalytes use isotope dilution/gas chromatography/mass spectrometry and requi re a mass spectrometer capable of making highly precise measurements of the ratio between the ion intensities of a characteristic ion from the analyte of interest and its stable-isotope-labeled analog. Recently the mass spect rometer used for 20 years for definitive method development and measurement s was replaced with a modern instrument capable of automated operation, wit h accompanying gains in convenience and sample throughput. Switching to the new instrument required modifications of measurement protocols, acceptance criteria, and ratio calculations with background corrections to go along w ith automated instrument operation. Results demonstrated that the two instr uments gave comparable results for measurements of both urea and cholestero l in samples from various serum-based Standard Reference Materials [SRMs] a nd College of American Pathologists materials.