Degradation kinetics of larotaxel and identification of its degradation products in alkaline condition

Abstract

Larotaxel, a new taxane compound prepared by partial synthesis from 10-deacetyl baccatin III, is active against tumors. In this research, a selective LC–MS method was developed and validated for the study of degradation kinetics of larotaxel, which was carried out in aqueous solutions with different pH (1.5, 3.0, 5.0, 6.5, 7.4, 9.0, 10 and 11.0) and temperature (0, 25, 37 and 45 °C). The linear range was 0.5–25 μg/mL, the intra- and inter-day precisions were less than 7.0%, and accuracy ranged from 97.4–104.5% for each analyte. The observed rate obtained by measuring the remaining intact larotaxel was shown to follow first-order kinetics. The activation energies for degradation were 126.7 and 87.01 kJ/mol at pH 1.5 and 11, respectively. Although larotaxel was stable in pH 5, 6.5 and 7.4 buffers at 37 °C for 24 h during our study, increasing or decreasing the pH of the solutions would decrease its stabilities. Moreover, three main degradation products in alkaline condition were separated by HPLC and identified by Q–TOF–MS. The three degradation products were confirmed as 10-deacetyl larotaxel, 7, 8-cyclopropyl baccatin Ⅲ and 10-deacetyl-7, 8-cyclopropyl baccatin Ⅲ.

Determination of solubility, stability and degradation kinetics of morin hydrate in physiological solutions

“…The minimum stability was found at pH 9.0 in all storage conditions. 26 In RT light condition, slightly similar stability was observed for pH 1.2, pH 5.0, pH 7.0 and pH 7.4 solvents.…”

“…The minimum stability was found at pH 9.0 in all storage conditions. 26 In RT light condition, slightly similar stability was observed for pH 1.2, pH 5.0, pH 7.0 and pH 7.4 solvents. In addition, regression coefficient (r 2 ) values and degradation rates of MH were calculated from the slope of the best-tted kinetic models.…”

“…Hence, all these results indicated the specific acid and base catalysed effect on MH stability. 26 From the r 2 values, we can also generalize trends in the drugs degradation rate and stability. The results indicated that the degradation rate was lower in acidic and neutral conditions than in basic medium.…”

Shelf Life Assessment of Picralima nitida and Glibenclamide Using Bio-Based Dose-Response Relationship Method

“…The higher the activation energies, E a , the lesser the influence of temperature on the degradation reaction. Based on the result, temperature contributed to the drugs' degradation [22] and the pharmacokinetic profile of the animal model also contributed to its degradation.…”

Determination of Shelf Life of Picralima nitida, Ciprofloxacin and Pefloxacin Using Bio-Based Concentration-activity Relationship Technique

“…The calculated activation energies E a for the degradation of the drug samples were found to be high (E a > 50 kJ/mol.K), as shown in Table 1. The higher the E a is, the less the degradation reaction is influenced by temperature; the result indicated that temperature contributed to the degradation of the drugs [44] but sensitivity activities to the bacteria also contributed to the degradation.…”