Degradation of dehydroascorbic acid in parenteral nutrition mixtures.

The degradation of ascorbic acid (AA) stored in parenteral nutrition (PN) regimens is initially by oxidation, catalysed by trace elements, in particular copper. After prolonged storage the concentration of AA remains relatively constant, with little variation, due to the lack of available oxygen. The initial degradation product is dehydroascorbic acid (DHAA). This is generated in an anaerobic environment, and is hypothesised to degrade by hydrolysis. It is the purpose of this investigation to ascertain the effect of temperature and trace elements on the anaerobic degradation of DHAA, and to identify the kinetics of the reaction. A stability-indicating reversed-phase HPLC assay was used. The column contained C(18) reverse-phase packing (Luna), mean diameter 5 microm. The column dimensions were 15 cm long with an internal diameter of 0.4 cm. The mobile phase consisted of methanol: phosphate buffer (pH 7.8: 0.067 mol dm(-3)) at a ratio of 40: 60 (v/v) and also included Cetrimide (mixed alkyltrimethylammonium bromide) (0.05 mol dm(-3)) as an ion pair reagent. The flow rate was 0.7 ml min(-1) and detection was by ultra-violet light absorption at 278 nm. This assay was used to monitor the degradation rate of DHAA in PN mixtures with and without trace elements over a range of temperatures (5-35 degrees C). Results indicated a first order reaction that was temperature-dependent but trace elements independent.

The photodegradation of vitamins A and E in parenteral nutrition mixtures during infusion.

BACKGROUND & AIMS: Vitamins A and E are the most light-sensitive vitamins. Vitamin A is degraded by photolysis, while vitamin E degrades by photo-oxidation. The composition of the parenteral nutrition mixture and the container could therefore influence degradation during daylight administration. The aim of this study was therefore to determine the influence of fat emulsion and the type of bag on the photo-degradation of vitamins A and E in Parenteral Nutrition (PN) mixtures during simulated infusion in daylight. METHODS: Representative adult PN mixtures, with and without fat emulsion, were prepared. Samples for analysis were taken from infusates and each bag during simulated infusion. Degradation of vitamins A and E was determined by stability-indicating HPLC analysis. RESULTS: Results indicated that vitamin A loss proceeded rapidly during infusion, resulting in up to 80% loss in 6 hours, even with light protection of the bag. The presence of fat emulsion did not provide significant light protection. Vitamin E degradation was substantial if mixtures were prepared in EVA bags but was largely prevented if PN mixtures were compounded and stored in multi-layered bags. CONCLUSIONS: It is recommended that all PN bags should be light-protected during infusion in daylight. The use of multi-layered bags will prevent vitamin E losses during infusion.

Compatibility and stability of additives in parenteral nutrition admixtures.

The addition of additives (electrolytes, trace elements, and vitamins) to parenteral nutrition (PN) mixtures can lead to precipitation as a result of physical incompatibilities and can lead to chemical degradation of individual ingredients. The most significant cause of precipitation is excessive concentrations of calcium phosphate. The most significant cause of chemical instability is the oxidation of specific vitamins. The factors influencing calcium phosphate solubility include the commercial amino acid source, the calcium and phosphate salts used, temperature, magnesium concentration, and final volume. Precipitation can be avoided by organic phosphates. Trace element precipitation is most commonly caused by the formation of iron phosphate salts or copper cysteinate in cysteine-containing amino acid infusions. The least stable nutrient is ascorbic acid, which reacts with oxygen, and is catalyzed by copper ions. Oxygen originates from PN ingredients, the filling process, air remaining in the bag after filling, and oxygen permeation through the bag wall. Storage in multilayered bags with reduced gas permeability can protect residual ascorbic acid. Other chemical losses are caused by the reduction of thiamine by metabisulfite, and photodegradation of daylight-sensitive vitamins, especially retinol and riboflavin, during administration.

The influence of amino acid source on the stability of ascorbic acid in TPN mixtures.

This study was undertaken to investigate the stability of ascorbic acid and its primary degradation product, dehydroascorbic acid, in total parenteral nutrition (TPN) mixtures. The influence of the type of bag and the commercial source of amino acid on ascorbate degradation was examined, using a stability-indicating high-pressure liquid chromatography (HPLC) method. Ascorbic acid was most stable in multilayered bags, compared with ethylvinyl acetate (EVA) bags. Results indicated that, in multilayered bags, the initial rapid ascorbic acid degradation was greatest in TPN mixtures containing amino acid infusions without reducing activity. In contrast, degradation in TPN mixtures containing amino acids with reducing compounds (Vamin 14 and Freamine III 8.5%) was less than 10% of the added amount. Dehydroascorbic acid degraded approximately in parallel with ascorbic acid, and it contributed to the total available ascorbate activity. The addition of air to TPN mixtures in multilayered bags caused accelerated degradation of both ascorbic acid and dehydroascorbic acid. It is concluded that TPN mixtures compounded in multilayered bags can be safely assigned extended shelf lives, especially if compounded using an amino acid with reducing activity. This is principally due to the protective effect of the bag wall in preventing oxygen transmission, the cause of ascorbic acid oxidation, because oxygen transmission through the bag wall is minimized during storage. TPN mixtures stored in EVA bags should be administered within 2-4 d of compounding, depending on the amino acid infusion used.

Precipitation of trace elements in parenteral nutrition mixtures.

Trace elements are an essential additive to parenteral nutrition (PN) mixtures. Previous studies have indicated that certain trace elements, in particular copper and iron, may interact with complete PN mixtures leading to precipitate formation. The causes of these incompatibilities have not been fully elucidated. The purpose of this study was to determine factors responsible for common trace element incompatibilities, using X-ray energy dispersive spectroscopy to examine the elemental content of precipitates isolated from stored PN mixtures with added trace elements. Results indicated that copper sulphide precipitated most rapidly in PN mixtures containing Vamin 9 and in mixtures stored in multilayered bags. Copper sulphide precipitation was delayed in PN mixtures containing Vamin 14 and was not observed in PN mixtures stored in EVA bags. Iron phosphate precipitates were observed in Synthamin-containing PN mixtures after storage, but this was prevented in mixtures containing vitamins stored in multilayered bags.

Stability of cocarboxylase in parenteral nutrition mixtures stored in multilayer bags.

The aim of this study was to determine the stability of cocarboxylase, a thiamine derivative employed as a vitamin B1 source in multivitamin additives, in parenteral nutrition (PN) mixtures containing different commercial amino acid infusions. In particular, the influence of a metabisulphite-containing amino acid product, Freamine III, was investigated. A liquid chromatographic assay method for cocarboxylase was developed and employed to investigate cocarboxylase degradation during extended storage of PN mixtures at 5 degrees C in multilayered bags. Results indicated that cocarboxylase was relatively stable over the 28-day storage period in PN mixtures containing Synthamin or Vamin products as amino acid source. In contrast, degradation was accelerated in PN mixtures containing Freamine III, suggesting that cocarboxylase is degraded by sodium metabisulphite, showing similar sensitivity to thiamine.

Long-term stability of cimetidine in total parenteral nutrition.

The stability of cimetidine (Tagamet) was investigated in total parenteral nutrition (TPN) mixtures containing different amino acid sources. TPN mixtures were stored at 5 degrees C in ethylvinyl acetate bags for 28 days and analysed by stability-indicating high-pressure liquid chromatography. Results indicated that cimetidine was physically compatible and chemically stable (less than 5% degradation) for at least 28 days in TPN mixtures containing either Freamine III, Vamin 14 or Aminoplex 12 as the amino acid source.

The stability of thiamine in total parenteral nutrition mixtures stored in EVA and multi-layered bags.

The compounding of complete total parenteral nutrition (TPN) mixtures into big bags with extended shelf-lives has been made more possible by the introduction of reduced gas permeable bags, using multi-layered plastic laminates. Since this produces a highly reduced chemical environment, the stability of thiamine; which degrades by reduction, may be compromised. It was the purpose of this study to investigate the degradation of thiamine at two different concentrations in TPN mixtures containing different commercial amino acid sources stored for extended periods in EVA or multi-layered bags. Results indicated that thiamine was unstable in mixtures containing Freamine III 8.5%, a metabisulphite-containing amino acid infusion, but was relatively stable in mixtures containing Vamin 14, Aminoplex 12 or Eloamin 15% as the amino acid source. Degradation of thiamine in Freamine III 8.5%-containing mixtures stored in multi-layered bags was more rapid than in EVA bags. Degradation rate was not greatly influenced by thiamine concentration. Results indicate that thiamine is stable in complete TPN mixtures for periods of at least 28 days in multi-layered bags, provided metabisulphite containing amino acid infusions are avoided. The shelf-life of complete mixtures containing Freamine III should be restricted to ensure patient receive minimum acceptable daily thiamine requirements.