Impact of Light Shielding on Photo-Degradation of Dacarbazine during the Preparation Process

Abstract

Dacarbazine (DTIC) is converted to the photo-degradation product 4-diazoimidazole-5-carboxamide (Diazo-IC) by light. Diazo-IC production is often responsible for the pain reactions observed during peripheral intravenous infusion of DTIC in clinical settings. Although light shielding during infusion decreases the photo-degradation of DTIC, its usefulness for the preparation of DTIC has not yet been fully clarified. The aim of this study was to investigate the light conditions during the preparation of DTIC solution in the compounding room from the viewpoint of the production amount of Diazo-IC. DTIC solution was prepared in the compounding room. Various light and temperature conditions and dissolving solutions during the preparation were investigated. The amounts of DTIC and Diazo-IC in solutions were determined using an HPLC coupled to UV detection. The photo-degradation of DTIC was estimated by the amount of Diazo-IC. Diazo-IC production in the dissolving solutions increased in a time-dependent manner at 4 and 25°C under light shielding. Light exposure during the dissolving process did not affect the DTIC and Diazo-IC concentrations. Light shielding during dissolution did not alter the Diazo-IC production until 4 h after dilution. In conclusion, short duration light exposure did not affect Diazo-IC production. These findings suggest that light shielding is not needed in the preparation of DTIC in the compounding room from the viewpoint of Diazo-IC production.

Anticancer Drugs: Recent Strategies to Improve Stability Profile, Pharmacokinetic and Pharmacodynamic Properties

“…These results have demonstrated that environmental matrices can produce different transformation products and that the experimental conditions in photodegradation studies are critical and should, therefore, be as similar as possible to those of environmental systems [ 81 ]. Dacarbazine, an alkylating agent commonly used in combination with other chemotherapeutic agents for the treatment of metastatic malignant melanomas, Hodgkin’s lymphoma and pheochromocytomas, is converted by light into 4-diazoimidazole-5-carboxamide [ 103 ]. This photo-transformation product is often responsible for the pain reactions observed during peripheral intravenous infusion during clinical application.…”

Single-Photon Deep-Red Light-Triggered Direct Release of an Anticancer Drug: An Investigative Tumor Regression Study on a Breast Cancer Spheroidal Tumor Model

“…Nevertheless, the most promising method for engineering programmable nanoscale drug delivery vehicles is to encode stimuli responsiveness and if the stimulus is external light stimuli, then photomanipulation will allow for spatial and temporal precision in drug delivery . Therefore, this class of drug delivery systems (DDSs) has recently acquired prominence in providing spatiotemporal control over the release of anticancer drugs at the tumor site upon light exposure . However, the inherent limitations of ultraviolet (UV) and visible light include low penetration depth, phototoxicity, insufficient photostability of the chromophore/fluorophore, and nonspecific background fluorescence, which limit its use in vivo.…”

Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation

“…DTIC is an anticancer drug indicated for the treatment of metastatic malignant melanoma and soft tissue sarcoma, being also used in the treatment of early Hodgkin lymphoma. , Although it may be ionized, this API is commercialized in a neutral form as an intravenous formulation, exhibiting pH-dependent aqueous solubility and a pronounced photodegradation when exposed to light. , The main photodegradation product, 2-azahypoxanthine (2-AZA), is pharmacologically inactive and further responsible for some adverse reactions. , To reduce photodegradation, freshly prepared DTIC solutions protected from light must be intravenously administered as quickly as possible. , Recently, Uchida et al developed a photochemically stabilized formulation of DTIC using reactive oxygen species. The lack of scientific reports on this line reinforces the idea that the emergence of alternative and safe technologies to overcome DTIC issues remains highly demanded.…”

“… 20 , 21 To reduce photodegradation, freshly prepared DTIC solutions protected from light must be intravenously administered as quickly as possible. 22 , 23 Recently, Uchida et al 24 developed a photochemically stabilized formulation of DTIC using reactive oxygen species. The lack of scientific reports on this line reinforces the idea that the emergence of alternative and safe technologies to overcome DTIC issues remains highly demanded.…”