Although multiple linear regression of docetaxel concentration for solutions stored in PABs revealed statistically significant differences in amount remaining as small as 2.4% between the 0.4 mg/mL and 0.8 mg/mL solutions, these differences were deemed to be of no practical difference in the evaluation of stability. Demonstrating a trend for the docetaxel concentration to decrease was considered more important than demonstrating a statistical difference in concentration between any 2 days. In fact, the random fluctuations in concentration around the initial concentration are not of practical importance and should be considered “noise” or experimental error, even though these differences, as small as 2.4%, were statistically significant. Linear regression indicated that the docetaxel concentration in a vial on day 21 and the docetaxel concentration in a PAB on day 35 was within 4% of the initial concentration and that deviations on any day did not exceed 5%. Assuming no degradation and assuming that all study day determinations represent estimates of an unchanging concentration, the interday reproducibility (expressed as CV) was 1.8% during the evaluation of storage in vials and 2.8% during the evaluation of storage in PABs. This is very similar to the interday reproducibility of 2.5% that was observed with the standards, which is equivalent to assay error.
Given that only small changes in docetaxel concentration were detected under these storage conditions, assurance of the specificity of the analytical method is very important. In addition to our demonstration that the method was accurate and reproducible, the specificity of the analytical method was demonstrated during the accelerated degradation studies (Figure 1). In these studies, a reduction in docetaxel concentration was observed as the concentration of apparent degradation products increased. Furthermore, the samples that we used for degradation at 80°C simulated closely our study samples (similar concentration and pH); therefore, the degradation process used here probably produced degradation products similar to those that would be produced in study samples over a prolonged period (e.g., several years). The separation and detection of intact drug in the presence of degradation compounds must be assured before the method can be considered suitable for indicating stability,10,11 as was shown here for docetaxel (see Figure 1).
The expiry dates determined in this study should be implemented in practice only after due consideration of sterility and the contamination rate of individual IV additive programs. Extension of the expiry date for this product beyond 4 h following dilution in NS is of considerable importance to efficiency. Extension of the docetaxel expiry date to 35 days in our IV additive service has eliminated wastage. cialis canadian pharmacy
In conclusion, vials of docetaxel diluted according to the manufacturer’s instructions to prepare a 10 mg/mL ethanol and polysorbate 80 solution retained more than 95% of their initial concentration when stored at either 4°C or 23°C for 21 days. In addition, docetaxel solutions that were further diluted with NS to concentrations of 0.4 or 0.8 mg/mL and stored in PABs at room temperature retained more than 95% of their initial concentration for 35 days.