title: Application of the reference method isotope dilution gas chromatography mass spectrometry (ID/GC/MS) to establish metrological traceability for calibration and control of blood glucose test systems.
abstract: Self-monitoring of blood glucose (BG) by means of handheld BG systems is a cornerstone in diabetes therapy. The aim of this article is to describe a procedure with proven traceability for calibration and evaluation of BG systems to guarantee reliable BG measurements. Isotope dilution gas chromatography mass spectrometry (ID/GC/MS) is a method that fulfills all requirements to be used in a higher-order reference measurement procedure. However, this method is not applicable for routine measurements because of the time-consuming sample preparation. A hexokinase method with perchloric acid (PCA) sample pretreatment is used in a measurement procedure for such purposes. This method is directly linked to the ID/GC/MS method by calibration with a glucose solution that has an ID/GC/MS-determined target value. BG systems are calibrated with whole blood samples. The glucose levels in such samples are analyzed by this ID/GC/MS-linked hexokinase method to establish traceability to higher-order reference material. For method comparison, the glucose concentrations in 577 whole blood samples were measured using the PCA-hexokinase method and the ID/GC/MS method; this resulted in a mean deviation of 0.1%. The mean deviation between BG levels measured in >500 valid whole blood samples with BG systems and the ID/GC/MS was 1.1%. BG systems allow a reliable glucose measurement if a true reference measurement procedure, with a noninterrupted traceability chain using ID/GC/MS linked hexokinase method for calibration of BG systems, is implemented. Systems should be calibrated by means of a traceable and defined measurement procedure to avoid bias.
authors.affiliation: Roche Diagnostics, Mannheim, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Andreis
authors.affiliation: Roche Diagnostics, Mannheim, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Küllmer
authors.affiliation: Roche Diagnostics, Mannheim, Germany matthias.appel@roche.com.
authors.forename: Matthias
authors.initials: M
authors.lastname: Appel
mesh_terms: D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring / Q000295:instrumentation* / Q000592:standards; D002138:Calibration; D002247:Carbon Isotopes; D008401:Gas Chromatography-Mass Spectrometry / Q000592:standards; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007201:Indicator Dilution Techniques / Q000592:standards; D011237:Predictive Value of Tests; D011934:Reagent Strips / Q000592:standards; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002247:Carbon Isotopes; D011934:Reagent Strips; D006593:Hexokinase
keywords: SMBG; accuracy; blood glucose monitoring; blood glucose monitoring systems; hexokinase; trueness