Adapted forms for administration to infants are limited. The proposed study was performed to propose oral liquid formulations of idebenone in Ora-Plus and either Ora-Sweet or Ora-Sweet SF, Ora-Blend, Ora-Blend SF and Inorpha. Each formulation was stored in 30 ml amber glass bottle at 5 or 25 °C for 90 days. Idebenone contents in these suspensions, determined by a stability-indicating high-performance liquid chromatography method, remained stable at least 90 days in Inorpha when stored at the two temperatures. In Ora-Blend, the stability was estimated at 14 days and in other suspensions at 20 days at the two temperatures. After 90 days storage, the pH of Ora-Plus and Ora-Sweet or Ora-Sweet SF changed between -0.10 and -0.25 units. For others suspensions, the pH changes were not significant (< -0.09 unit). No change was observed in color, odor or visual microbiology. To conclude, we recommended the use of idebenone in Inorpha vehicle stable for at least 90 days at 25 °C.
To ensure motionless conditions during computed tomography or magnetic resonance imaging in infants, sedative drugs could be used but with the potential risk of adverse effects such as respiratory depression. 1 Pentobarbital sodium (Nembutal) and chloral hydrate are the more frequently used drugs. 2 Clinical studies reported the effectiveness of pentobarbital sedation and a decreased rate of adverse events as compared with chloral hydrate for imaging sedative procedures. 3 Pentobarbital is usually administered to infants at the dose of 4 to 5 mg/kg, with a maximum of 8 mg/kg. 3 Nembutal is not available in the United States and Europe, and some hospital pharmacy units prepare rectal or oral forms. To facilitate its administration, we chose to study pentobarbital sodium stability in water and compounded in 5 suspensions. Methods Pentobarbital sodium powder (Inresa, Bartenheim, France) was used to prepare 6 different suspensions at 25 mg/mL in deionized water (Fresenius,
A stability-indicating assay by reversed-phase high performance liquid chromatography method was developed and validated for the determination of sulthiame (STM). The chromatographic separation was achieved on a reversed-phase NovaPack C18 column and an isocratic mobile phase consisting of deionized water:methanol (70:30, v/v). The flow rate was 1.0 mL/min (ultraviolet detection at 210 nm). The STM was separated within 2.83 min. The linearity of the method was demonstrated in the range of 20.0–200.0 μg/mL and a coefficient of determination of r2 = 0.9999. The limits of detection and quantification were 4.2 and 9.5 μg/mL, respectively. The intraday and interday precisions were less than 1%. Accuracy of the method ranged from 98.3% to 101.7%, with a relative standard deviation of <1%. STM was degraded by accelerated breakdown in alkaline, acidic, or oxidative stress conditions. This method allows accurate and reliable determination of STM for drug stability assay in pharmaceutical studies.
Background
Due to repetitive and tedious handling tasks, production of anticancer drugs for infusion is associated with a high risk of non-conformity. Thus, on-line quality control is necessary to improve the quality of preparation. Since the quantities produced are ever growing, very fast analytical methods of control are needed to minimise the delay before release.
PurposeA high-performance liquid chromatography method has been developed for quality control of vinca alkaloid infusion bags (vindesine, vincristine, vinorelbine and vinblastine).
Materials and Methods
The separation was optimised by a Doehlert experimental design using a mixture of those 4 alkaloids. Chromatography was performed using Prostar Varian chromatographic equipment with a Photodiode array Detector. A short Polaris C18 column (3 µm, 50 mm × 4.6 mm) was used for all separations. The optimization varied 3 parameters: pH of the phosphate buffer 25 mM (7.0–7.6), flow rate of the mobile phase (0.7–1.3 mL.min−1) and proportion of acetonitrile (47–53%). 36 trials were necessary. The target response was the shortest run time giving a minimal resolution score of 1.5 for the most critical pair of peaks.
Results
For vinorelbine, pH had a major effect on resolution. Optimal resolutions were obtained with a pH of 7.25. Then, the flow rate was set at 1.6 mL.min−1 with a mobile phase consisting of water-acetonitrile (47–53 v/v). Under these conditions, resolution was at least 1.6 with an analysis time less than 2.0 min. Retention times were 1.03, 1.27, 1.39 and 1.68 minutes for vindesine, vincristine, vinblastine and vinorelbine respectively. Methods were validated according to ICH criteria and are now routinely used without troubleshooting.
Conclusions
This method allows in-line quality control of 4 vinca alkaloids in a very short time (less than 2 minutes) and constitutes a suitable and safe tool for chemotherapy preparation.
No conflict of interest.
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