Compatible stability of methylprednisolone sodium succinate and tropisetron in 0.9% sodium chloride injection.

Background: A combination of methylprednisolone sodium succinate and tropisetron hydrochloride is commonly used to treat the nausea and vomiting associated with antineoplastic therapy. The objective of this study was to investigate the stability of tropisetron hydrochloride and methylprednisolone sodium succinate in 0.9% sodium chloride injection for up to 48 hours. Methods: Commercial solutions of methylprednisolone sodium succinate and tropisetron hydrochloride were obtained and further diluted with 0.9% sodium chloride injection to final concentrations of either 0.4 or 0.8 mg/mL (methylprednisolone sodium succinate) and 0.05 mg/mL (tropisetron). The admixtures were assessed for periods of up to 48 hours after storage at 4°C with protection from light and at 25°C without protection from light. Physical compatibility was determined visually, and the chemical compatibility was measured with high-performance liquid chromatography (HPLC) and by measurement of pH values. Results: HPLC analysis demonstrated that methylprednisolone sodium succinate and tropisetron hydrochloride in the various solutions were maintained at 97% of the initial concentrations or higher during the testing period. There were no changes observed by physical precipitation or pH in any of the prepared solutions. Conclusions: Tropisetron hydrochloride injection and methylprednisolone sodium succinate injection in 0.9% sodium chloride injection are stable for up to 48 hours at 4°C and 25°C.

Determination of some antiemetic drugs through its native fluorescence or fluorescence quenching of cerrous ammonium sulphate.

The manuscript describes two fluorimetric methods for the determination of some antiemetic drugs namely granisetron HCl, ondansetron HCl and tropisetron HCl, used in the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. Granisetron HCl solution exhibits a native fluorescence, which can be applied for its determination at 365 nm upon excitation at 305 nm. The method was applied for the determination of granisetron HCl in drug substance, drug product as well as in presence of its acid induced degradation products. The quantum yield was calculated. The second proposed method is based on measuring the quenching effect induced by ondansetron HCl or tropisetron HCl on the fluorescence intensity of cerrous ammonium sulphate at λem 348 nm upon excitation at 250 nm in acidic medium. The analysis of quenching data showed that quenching of cerrous ammonium sulphate induced by ondansetron HCl or tropisetron HCl is mainly through dynamic quenching. Various variables affecting fluorescence response were studied and optimized. The obtained results were found to be statistically agreed with those obtained from the official or reported ones. Moreover, the validity of the methods was assessed according to ICH guidelines.

Compatibility and stability of dezocine and tropisetron in 0.9% sodium chloride injection for patient-controlled analgesia administration.

Tropisetron is an adjuvant for dezocine used in intravenous patient-controlled analgesia (PCA) and has been reported to provide superior pain control. It is efficacious in reducing the institutional incidence of postoperative nausea and vomiting (PONV), which decreases resource utilization and cost. However, no scientific evidence has been reported in the literature demonstrating analytical confirmation of the compatibility and stability of the combination of dezocine and tropisetron. Thus, the present study aimed to investigate the stability of dezocine with tropisetron in 0.9% sodium chloride injection form for PCA administration.Commercial solutions of dezocine and tropisetron were combined and examined for compatibility and stability when diluted with 0.9% sodium chloride injection in polyolefin bags and glass bottles stored at 4°C or 25°C for up to 14 days. The initial concentrations were 40 mg/100 mL dezocine and 5 mg/100 mL tropisetron. For all samples, the compatibility parameters (including precipitation, cloudiness, discoloration, and pH values) were evaluated. Chemical stability was also determined using high-performance liquid chromatographic (HPLC) analysis.After a 14-day period of storage at 4°C or 25°C, the initial concentrations of dezocine and tropisetron were maintained at at least 98%. All of the mixtures remained clear and colorless throughout the observation period, and no color change or precipitation was observed.These results indicated that admixtures of 40 mg/100 mL dezocine and 5 mg/100 mL tropisetron in 0.9% sodium chloride injection were stable for at least 14 days when stored in polyolefin bags or glass bottles at 4°C or 25°C and protected from light.

Conformational transitions of the serotonin 5-HT3 receptor.

The serotonin 5-HT3 receptor is a pentameric ligand-gated ion channel (pLGIC). It belongs to a large family of receptors that function as allosteric signal transducers across the plasma membrane1,2; upon binding of neurotransmitter molecules to extracellular sites, the receptors undergo complex conformational transitions that result in transient opening of a pore permeable to ions. 5-HT3 receptors are therapeutic targets for emesis and nausea, irritable bowel syndrome and depression3. In spite of several reported pLGIC structures4-8, no clear unifying view has emerged on the conformational transitions involved in channel gating. Here we report four cryo-electron microscopy structures of the full-length mouse 5-HT3 receptor in complex with the anti-emetic drug tropisetron, with serotonin, and with serotonin and a positive allosteric modulator, at resolutions ranging from 3.2 Å to 4.5 Å. The tropisetron-bound structure resembles those obtained with an inhibitory nanobody5 or without ligand9. The other structures include an 'open' state and two ligand-bound states. We present computational insights into the dynamics of the structures, their pore hydration and free-energy profiles, and characterize movements at the gate level and cation accessibility in the pore. Together, these data deepen our understanding of the gating mechanism of pLGICs and capture ligand binding in unprecedented detail.