The Chemical Contamination In Glucose Containing Sterile Fluids

Abstract

This work is to study the chemical contamination in medical glucose fluids, that are produced by the formation of glucose degradation products during the heat sterilization cycle. Fourteen glucose fluids are subjected to this study, which include intravenous infusions, a peritoneal dialysis fluid, also it include the study of the various electrolytes that used in these fluids. A group of sample was sterilized by microbial filtration and used as control. Another samples were sterilized by one heat sterilization cycle. In some samples the heat sterilization cycle is repeated from two to six cycles. The study depend on measuring: 1- The main glucose degradation product, 5. hydroxy methyl furfural (5HMF). Which absorbed at 284 nm, and an intermediate degradation product (P1) which absorbed at 228 nm. 2- pH value . 3- The optical rotation (α) 4- Color intensity 5- Toxicity testing by using a cell growth inhibition method. The solutions that sterilized by microbial filtration found to contain 0.019 mM 5HMF in the 5% glucose solutions. The 5HMF increases by increasing glucose concentration to 0.19 mM in the 50% glucose solution. By the heat sterilization cycle, 5HMF increases in all glucose solutions studied and the highest amount was 48.45 mM which found in glucose 50% after six sterilization cycles. The absorbance due to the intermediate compound Ap1 at 228 nm in the microbial filtered solution was ≤ 0.005. By the heat sterilization cycle Ap1 increases in all test solutions. Ap1 was very high in the heat sterilized glucose solutions that contain sodium acetate or sodium lactate. Also Ap1 was high in the heat sterilized solutions that contain Mgcl2. The pH value reduces by the heat sterilization cycle and the solutions become more acidic. The color is changed by the heat sterilization cycle. Although any solution that it is glucose concretion is ≤ 10% and not contain sodium acetate or sodium lactate is considered as colorless solution even by repeating the sterilization cycle six times. While such solutions, glucose concentration ≥ 20%, or contain sodium acetate and sodium lactate, they obtain a high color intensity with the heat sterilization cycle and repetition of the cycle from yellow to dark brown. The optical rotation (α) was reduced by the heat sterilization cycle in all test solutions. The decrease in the optical rotation found to be very large in solutions that contain sodium acetate and sodium lactate. The sterile filtered solutions cause ≤ 2.6% cell growth inhibition, except the concentrated glucose solutions 20%, 40% and glucose 50%. Which they cause 32%, 98.39% and 98.9% cell growth inhibition respectively. By the heat sterilization cycle the effect of cell growth inhibition increased in all test solutions. The cell growth inhibition increased by the heat sterilization cycle, glucose concentration and all electrolytes except Hcl and Nacl. It is found that there is no relationship between the cell growth inhibition and 5HMF nor the pH value. The correlation coefficients [r] = 0.33 and 0.20 respectively. While there is a strong relationship between the cell growth inhibition and the intermediate degradation product p1, [r] = 0.76. a very strong relationship is found between the cell growth inhibition and glucose concentration, [r] = 0.89 . The preparation, sterilization and the chemical analysis of the fluids were done in Balsam pharmaceutical company. While the in vitro toxicity testing was done in the Animal Resources Research corporation.