Evaluation of UV-light-shielding bags efficiency on dacarbazine photodegradation
5 October 2022
M. Sangnier1, J-M. Bernadou1, M. Noguero1, G. Bouguéon1,2, A. Berroneau1, S. Crauste-Manciet1,21 Pharmaceutical Technology Department, Bordeaux University Hospital, Avenue de Magellan, 33604 Pessac, France
2 ARNA Laboratoire ChemBioPharm U1212 INSERM - UMR 5320 CNRS, Université de Bordeaux, France
Dacarbazine (DCZ) is an antineoplastic drug administered by intravenous infusion for melanoma and Hodgkin disease treatment known to be rapidly degraded under light. A case of a DCZ bag turning pink after exposure to sunlight when being administered raised questions about the efficiency of the UV-light-shielding bags used. It is also important to notice that photodegradation products of DCZ are suspected to be responsible for side effects like pain reactions during infusion [1]. The aim of this preliminary study was to find if UV-light-shielding bags were efficient against dacarbazine photodegradation and if other protective bags were more efficient.
A forced degradation test was done for 1.27mg/ml DCZ. Bags were exposed to fluorescent light at room temperature for 24h: (a) in classic protective bag, (b) in UV-light-shielding bag, (c) in opaque bag OPABAG (BBRAUN) and (d) in opaque bag O-PACK (SLB). One bag was placed in complete darkness (e) and sampled at the same times.
Color change was observed visually and samples were collected at 0, 6, 10, 14, 18, 22 and 24h for HPLC dosage to find degradation products. HPLC method was adapted after Shetty et.al [2] (C18; phosphate buffer 0.05M pH7 + triethylamine 0.04M; acetonitrile 90/10; 1ml/min; 20 min long analysis).
A pink coloration was observed at t=16h for bag (a) and (b) and no coloration was observed on bags (c), (d) and (e) after 24 hours. For all the bags, a degradation peak at 4.362 min, not present at initial dosage t0 was observed from t=6h. The reduction of degradation product AUC with opaque bags was 42.2% for bag (c) and 49.8% for bag (d) compared with a classic bag. In comparison with initial DCZ peak AUC at t0, it was reduced by 5.68% for bag (a), 8.45% for bag (b), 2.48% for bag (c) and 2.78% for bag (d). Degradation of DCZ with opaque bags was therefore lower by 56% (c) and 51% (d) compared with classic bags. The degradation in opaque bags is similar to the degradation in complete darkness.
According to literature, the product responsible for the color change and the one detected by HPLC may be two different photodegradation products, which confirms that DCZ undergoes degradation when exposed to fluorescent light. Degradation is observed even in the dark because the stability of DCZ is better at refrigerated temperatures, test must be performed. Comparison of different protective bags shows that opaque bags protect better against photodegradation than UV-light-shielding bags which seem to have no benefits compared with classic bags. Further studies are needed to identify the degradation product, to perform these tests on a larger number of bags and to compare natural and artificial light.
[1] Shetty, B. V., Schowen, R. L., Slavik, M., & Riley, C. M. (1992). Degradation of dacarbazine in aqueous solution. Journal of Pharmaceutical and Biomedical Analysis, 10(9), 675‑683.