Quantification of Degradation Products Formed during Heat Sterilization of Glucose Solutions by LC-MS/MS: Impact of Autoclaving Temperature and Duration on Degradation.

Sarah Leitzen,Michael Steffens,Matthias Vogel,Martin Brandl,Thomas Zapf,Christa Elisabeth Müller

doi:10.3390/ph14111121

Abstract

Heat sterilization of glucose solutions can lead to the formation of various glucose degradation products (GDPs) due to oxidation, hydrolysis, and dehydration. GDPs can have toxic effects after parenteral administration due to their high reactivity. In this study, the application of the F0 concept to modify specific time/temperature models during heat sterilization and their influence on the formation of GDPs in parenteral glucose solutions was investigated using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Glucose solutions (10%, w/v) were autoclaved at 111 °C, 116 °C, and 121 °C for different durations. The GDPs glyoxal, methylglyoxal, glucosone, 3-deoxyglucosone/3-deoxygalactosone, 3,4-dideoxyglucosone-3-ene, and 5-hydroxymethylfurfural were quantified after derivatization with o-phenylenediamine by an optimized LC-MS/MS method. For all GDPs, the limit of detection was <0.078 μg/mL, and the limit of quantification was <0.236 μg/mL. The autoclaving time of 121 °C and 15 min resulted in the lowest levels of 3-DG/3-DGal and 5-HMF, but in the highest levels of GO and 2-KDG. The proposed LC-MS/MS method is rapid and sensitive. So far, only 5-HMF concentrations are limited by the regulatory authorities. Our results suggest reconsidering the impurity limits of various GDPs, especially the more toxic ones such as GO and MGO, by the Pharmacopoeias.

Highlights

Sterile glucose infusion solutions for parenteral administration are commonly used as reconstitution solvents or diluents for injectable drugs and for peritoneal dialysis [1].The sterility of the parenteral glucose solutions is a crucial prerequisite for their safety.Sterility can be achieved via several methods and conditions
In order to guarantee the sterility of steam-sterilized glucose solutions, the European Pharmacopoeia stipulates that the products to be steam-sterilized must be heated to at least 121 ◦ C for 15 min
Since the 10% (w/v) glucose solutions are of particular interest with regard to their use as carrier solutions for electrolytes and drugs, we wanted to examine these solutions in more detail [20]

Summary

Introduction

Sterile glucose infusion solutions for parenteral administration are commonly used as reconstitution solvents or diluents for injectable drugs and for peritoneal dialysis [1].The sterility of the parenteral glucose solutions is a crucial prerequisite for their safety.Sterility can be achieved via several methods and conditions. In order to guarantee the sterility of steam-sterilized glucose solutions, the European Pharmacopoeia stipulates that the products to be steam-sterilized must be heated to at least 121 ◦ C for 15 min (reference sterilization procedure). Other combinations of time and temperature may be used if they achieve a sterility assurance level (SAL) of 10−6 or less. This process is to be controlled with the guide germ Geobacillus stearothermophilus [2]. The F0 concept is considered to be an equivalent sterilization process; this refers to processes that achieve a comparably lethal effect with different temperature and time combinations as the reference sterilization process described in the European Pharmacopoeia.

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