Stability of azasetron-dexamethasone mixture for chemotherapy-induced nausea and vomiting administration

Abstract

Combination antiemetic therapy has become common practice for the prevention of nausea and vomiting caused by anticancer drugs. In this study, we investigated the stability of azasetron hydrochloride 0.1 mg/mL plus dexamethasone sodium phosphate 0.05, 0.1, or 0.2 mg/mL in 0.9% sodium chloride injection and stored in polyolefin bags and glass bottles over a period of 14 days at 4°C and 48 hours at 25°C. The stability studies were evaluated by visual inspection, pH measurement, and a high-pressure liquid chromatography assay of drug concentrations. During the study period, the concentration of each drug in the various solutions remained above 97% of the initial concentration at both 4°C and 25°C when protected from room light. Under the condition of 25°C with exposure to room light, the concentrations of both drugs were significantly lowered over 48 hours. The pH value decreased, and the color changed from colorless to pink. Our study demonstrates that the azasetron-dexamethasone mixture at a clinically relevant concentration seems to be stable for 48 hours at 25°C and for 14 days at 4°C when packaged in polyolefin bags or glass bottles and protected from room light. The room light is the main influential factor on stability. Clinicians should be aware that combinations of azasetron hydrochloride and dexamethasone sodium phosphate in solution with light exposure should be avoided.

Compatibility and Physical Properties of Dexamethasone-Ondansetron Intravenous Admixture

“…Therefore, the IV admixture of DEX and OND should be avoided if benzyl alcohol was used as a preservative in the commercial product. Previous investigations had highlighted the impact of various parameters on the compatibility and stability of DEX and OND or other serotonin 5-HT 3 receptor antagonists IV admixtures, such as diluents, 6,18 storage conditions -container and temperature, 7 preservatives, 8 light exposure, 19 amongst others. The present work delineates in particular, the importance of the concentration of the individual components as well as the final volume on the compatibility of the IV admixture, thereby providing new insight relevant to the safe coadministration of these antiemetics.…”

A Fast and Validated HPLC Method for the Simultaneous Analysis of Five 5-HT3 Receptor Antagonists via the Quantitative Analysis of Multicomponents by a Single Marker

“…According to the literature [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24], acetonitrile and acidic water media were selected to optimize the mobile phase composition. A series of concentrations, pH values, the ratio of aqueous potassium dihydrogen phosphate solution, and different chromatographic column types were studied to ensure good resolution and appropriate retention time of the five 5-HT 3 receptor antagonists.…”

“…HPLC is commonly used to verify rapid detection systems due to its attractive features, such as high peak efficiencies, great resolution, high sensitivity, good repeatability, and wide application range. HPLC analytic methods for the detection of 5-HT 3 receptor antagonists such as ODT, GNT, TPT, AZT, and RMT are already mature, and most of them use retention data in the qualitative analysis, while the external standard method (ESM) is applicable in quantitative analysis [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. However, some of these methods may take a long time, and the specific drugs to be tested must correspond to reference substances, which cannot meet the requirements of rapid drug detection.…”

Catalyst free synthesis of 2‐Aryl‐2H‐benzo[b][1,4]oxazines and 3‐Aryl‐2H‐benzo[b][1,4]thiazin‐2‐ones: An ultrasonication‐assisted strategy

“…1,4-Benzoxazine motif constitutes an intrinsic part of a large class of heterocyclic constructs with a cosmopolitan distribution in drugs, bioactive agents, and a wide range of natural products. [1][2][3][4] Antibiotic drug, levofloxacin, [5] serotonin 3 receptor antagonist, azasetron, [6] neuroprotective synthetic compound HSB-13 [7] and natural products like pitucamycin and dandamycin [8] are some of the commonly encountered examples harboring this important structural construct. A rare tetracyclic natural product based on bis-benzoxazine motif was also recently isolated from a co-culture of sponge-associated actinomycetes.…”

“…Keeping into consideration the ubiquitous nature of 1,4-benzoxazines and their wide range of biological activities, [1][2][3][4][5][6][7][8][9] an ample number of synthetic methods have been developed toward this end. Traditional synthesis of 1,4-benzoxazine derivatives involves multistep processes, using 2-nitrophenols or 2-aminophenols as the starting materials.…”