A study of the stability of ascorbic acid in parenteral nutrition mixtures
Parenteral nutrition (PN) is a method of feeding those incapable of absorbing nutrients
from the gastrointestinal tract. All required nutrients are combined in one "big bag".
Consequently, many chemical interactions are possible between components.
Ascorbic acid (AA) is ubiquitous to both animal and plant kingdoms. Although its
biochemistry is not fully understood, dietary deficiency is detrimental to well being, with
the most extreme condition being scurvy. AA is water-soluble and frequent intake is
therefore required to maintain nutritional status.
AA is possibly the most reactive additive in PN mixtures, readily reacting with dissolved
oxygen, initially producing dehydroascorbic acid (OHAA). OHAA retains the biological
activity of AA. It was the purpose of this study to further knowledge regarding stability of
AA and OHAA in PN mixtures, informing pharmaceutical practice to improve safety and
efficacy of PN.
A stability-indicating HPLC method was optimised for the study of AA and OHAA in PN
mixtures. A study of the kinetics of OHAA degradation was undertaken to provide data
that could be used to predict OHAA stability. Results obtained indicated a first order reaction. In direct contrast to AA degradation, trace elements did not catalyse OHAA
A further product of AA degradation is oxalic acid (OA) which is potentially toxic. A HPLC method for the determination of OA in PN mixtures was developed and validated, although
minimum quantification limits were relatively high (~10J.Lg/ml).The method was used to assess OA appearance in stored PN mixtures, with results indicating that concentrations
remained below 10J.Lg/ml even after 35 days storage.
The final aspect of this research was to investigate the most likely components of a PN
mixture which may "protect" AA from oxidation. a-tocopherol photo-oxidises and
therefore may compete with AA for oxygen. As light catalyses the reaction it is possible oxygen reacts more rapidly with a-tocopherol compared with AA. Results indicated 0.-
Tocopherol did not oxidise in preference to AA and therefore offered no "protection".
Cysteine is a reducing agent included in some amino acid preparations. The average
dissolved oxygen content of standard adult PN mixtures was determined, from which the amount of cysteine required to react with dissolved oxygen was calculated. AA instability
in PN mixtures was compared with and without cysteine. Results indicated that adding
cysteine to PN mixtures 24 hours before addition of AA, resulted in retention of >95% AA.
Results obtained from this study have furthered knowledge of the AA degradation profile,
its kinetics and the potential influence of other components in PN mixtures. In particular
potential strategies for minimising AA degradation are identified therefore ensuring
patients receive quantities approaching those prescribed.