title: Temperature: the single most important factor for degradation of glucose fluids during storage.
abstract: OBJECTIVE
  Bioincompatible glucose degradation products (GDPs) develop during heat sterilization of peritoneal dialysis (PD) fluids. However, degradation may also take place during storage. Consequently, storage may add to the bioincompatibility caused by heat sterilization. The aim of the present study was to investigate how different factors such as the sterilization procedure, pH, glucose concentration, and temperature influence GDP production during storage.
  
  
  METHODS
  Degradation in glucose solutions was followed by pH and UV absorbance at 228 nm and 284 nm over 2 years of storage. Different sterilization times, storage temperatures, pH, and glucose concentrations were included in the study. Peritoneal dialysis fluids were also used in the experiment. Bioincompatibility was estimated through inhibition of cell growth in L-929 fibroblasts, and GDPs through UV absorption and liquid chromatography.
  
  
  RESULTS
  The most important factor determining the rate of GDP production during storage was temperature. The GDPs created by heat sterilization promoted further degradation of glucose during subsequent storage. A pH of around 3.2 protected glucose from degradation during both heat sterilization and storage. At a storage temperature of 20 degrees C and a pH of 3.2, degradation was almost negligible. Heat sterilization produced considerable amounts of GDPs absorbing at 228 nm. During initial storage, these 228 nm-absorbing GDPs almost disappeared. After reaching a nadir, absorbance at 228 nm again started to increase. Contrary to this, absorbance at 284 nm [caused mainly by 5-hydroxymethyl-2-furaldehyde (5-HMF)] increased during the whole storage period. After 2 years at 40 degrees C, the concentrations of GDPs produced during storage were of the same magnitude as those caused by heat sterilization. Inhibition of cell growth of L-929 fibroblasts correlated well with the part of the absorbance at 228 nm not caused by 5-HMF in glucose solutions that were heat sterilized under a wide range of conditions. This part of 228 nm absorbance (denoted 228corr) was caused almost entirely by 3,4-dideoxyglucosone-3-ene (3,4-DGE).
  
  
  CONCLUSIONS
  Temperature is the single most important factor for glucose degradation during storage. The concentrations of bioincompatible GDPs produced may, under improper conditions, be as high as those produced during sterilization. High concentrations of glucose and low pH protect glucose from being degraded during both sterilization and storage. A good estimate of 3,4-DGE concentration in the fluids can be obtained correcting the UV absorbance at 228 nm for the influence from 5-HMF (and, when appropriate, for lactate). The 228corr may thus be used as a simple quality control for the fluids.
authors.affiliation: Gambro AB, Lund, Sweden. pk@gambro.com
authors.forename: Per
authors.initials: P
authors.lastname: Kjellstrand
authors.forename: Martin
authors.initials: M
authors.lastname: Erixon
authors.forename: Anders
authors.initials: A
authors.lastname: Wieslander
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lindén
authors.forename: Evi
authors.initials: E
authors.lastname: Martinson
mesh_terms: D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D015314:Dialysis Solutions / Q000378:metabolism*; D004355:Drug Stability; D004356:Drug Storage; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D013056:Spectrophotometry, Ultraviolet; D013242:Sterilization
chemical_list: D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced; D006131:Growth Inhibitors; C008046:5-hydroxymethylfurfural; D003847:Deoxyglucose; D005662:Furaldehyde; C016350:3-deoxyglucosone; D005947:Glucose