title: [Validation of pharmaceutical quality of a [6,6-(2)H(2)]-glucose parenteral solution used for insulin-resistance measurement during human clinical trials].
abstract: BACKGROUND
  Deuterated glucose ([6,6-(2)H(2)]-glucose) is a stable isotopic tracer administered parenterally in healthy volunteers, obese or diabetic patients in clinical trial to study glucose metabolism during euglycemic hyperinsulinemic clamps. In accordance with the Health Authorities on drug safety, we evaluated the pharmaceutical quality of this preparation for biomedical research with a stability study.
  
  
  METHODS
  After pharmaceutical qualification of the raw material, the [6,6-(2)H(2)]-glucose was dissolved in water for injection, then sterile, filtered under positive pressure of nitrogen and then autoclaved. Two batch products (500mg/10mL and 2g/15mL) were sampled to evaluate glucose alteration, isotope shift, limpidity, apyrogenicity and sterility at regular intervals for 2 years. Deuterated glucose solutions were stored in the dark, at +2°C+8°C, in type II glass bottles.
  
  
  RESULTS
  Neither significant decrease of glucose concentration nor pH variation were observed for 2 years. The 5-hydroxymethylfurfural concentration was below the human harmful levels, attesting a non-generation of metabolites during autoclaving. Isotopic enrichment higher than 99% reflected the stability of deuterated label on the 6-carbon of glucose molecules. The non-visible particle concentration below the minimal permissible concentration tolerated by the European Pharmacopoeia and the absence of bacterial endotoxin and bacterial growth attested limpidity, apyrogenicity and sterility of the [6,6-(2)H(2)]-glucose solutions.
  
  
  CONCLUSIONS
  After the 2-year study, 500mg/10mL and 2g/15mL deuterated glucose solutions stored in the dark at +2°C+8°C were stable in aqueous solution, allowing to ensure safety administration for human clinical trials using euglycemic hyperinsulinemic clamps.
authors: Inserm U1060, laboratoires Carmen, Inra 1235, centre de recherche en nutrition humaine Rhône-Alpes, centre européen nutrition santé (CENS), hospices civils de Lyon, centre hospitalier Lyon-Sud, université Claude-Bernard Lyon-1, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France. emilie.blond@chu-lyon.fr
authors: E
authors: E
authors: Blond
authors: E
authors: E
authors: Diouf
authors: M-L
authors: ML
authors: Tall
authors: V
authors: V
authors: Sauvinet
authors: M
authors: M
authors: Desage
authors: M-C
authors: MC
authors: Despiau
authors: M
authors: M
authors: Laville
authors: F
authors: F
authors: Pirot
authors: J
authors: J
authors: Goudable
authors: C
authors: C
authors: Pivot
mesh_terms: D002986:Clinical Trials as Topic; D003903:Deuterium; D004339:Drug Compounding; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D005374:Filtration; D005947:Glucose / Q000592:standards*; D015309:Glucose Clamp Technique; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007263:Infusions, Parenteral; D007333:Insulin Resistance / Q000502:physiology*; D019275:Radiopharmaceuticals / Q000592:standards*; D015203:Reproducibility of Results; D012996:Solutions / Q000592:standards; D013242:Sterilization
chemical_list: D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D012996:Solutions; D003903:Deuterium; D005947:Glucose