title: Development and Validation of a Rapid (13)C6-Glucose Isotope Dilution UPLC-MRM Mass Spectrometry Method for Use in Determining System Accuracy and Performance of Blood Glucose Monitoring Devices.
abstract: BACKGROUND
  There is currently considerable discussion about the accuracy of blood glucose concentrations determined by personal blood glucose monitoring systems (BGMS). To date, the FDA has allowed new BGMS to demonstrate accuracy in reference to other glucose measurement systems that use the same or similar enzymatic-based methods to determine glucose concentration. These types of reference measurement procedures are only comparative in nature and are subject to the same potential sources of error in measurement and system perturbations as the device under evaluation. It would be ideal to have a completely orthogonal primary method that could serve as a true standard reference measurement procedure for establishing the accuracy of new BGMS.
  
  
  METHODS
  An isotope-dilution liquid chromatography/mass spectrometry (ID-UPLC-MRM) assay was developed using (13)C6-glucose as a stable isotope analogue to specifically measure glucose concentration in human plasma, and validated for use against NIST standard reference materials, and against fresh isolates of whole blood and plasma into which exogenous glucose had been spiked. Assay performance was quantified to NIST-traceable dry weight measures for both glucose and (13)C6-glucose.
  
  
  RESULTS
  The newly developed assay method was shown to be rapid, highly specific, sensitive, accurate, and precise for measuring plasma glucose levels. The assay displayed sufficient dynamic range and linearity to measure across the range of both normal and diabetic blood glucose levels. Assay performance was measured to within the same uncertainty levels (<1%) as the NIST definitive method for glucose measurement in human serum.
  
  
  CONCLUSIONS
  The newly developed ID UPLC-MRM assay can serve as a validated reference measurement procedure to which new BGMS can be assessed for glucose measurement performance.
authors.affiliation: Proteomics Programmatic Core Laboratory, Houston Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Risë K
authors.initials: RK
authors.lastname: Matsunami
authors.affiliation: Livongo Health, Palo Alto, CA, USA kangelides@livongo.com.
authors.forename: Kimon
authors.initials: K
authors.lastname: Angelides
authors.affiliation: Proteomics Programmatic Core Laboratory, Houston Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Engler
mesh_terms: D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D007201:Indicator Dilution Techniques; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001786:Blood Glucose
keywords: accuracy; blood glucose; blood glucose meter; glucose reference measurement procedure; isotope dilution mass spectrometry; standardization