Liquid chromatography mass spectrometry simultaneous determination of vindoline and catharanthine in rat plasma and its application to a pharmacokinetic study

Vinblastine and vincristine, both of which are bisindole alkaloids derived from vindoline and catharanthine, have been used for cancer chemotherapy; their monomeric precursor molecules are vindoline and catharanthine. A simple and selective liquid chromatography mass spectrometry method for simultaneous determination of vindoline and catharanthine in rat plasma was developed. Chromatographic separation was achieved on a C₁₈ (2.1 × 50 mm, 3.5 µm) column with acetonitrile–0.1% formic acid in water as mobile phase with gradient elution. The flow rate was set at 0.4 mL/min. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification. Mean recoveries were in the range of 87.3–92.6% for vindoline in rat plasma and 88.5–96.5% for catharanthine. Matrix effects for vindoline and catharanthine were measured to be between 95.3 and 104.7%. Coefficients of variation of intra‐day and inter‐day precision were both <15%. The accuracy of the method ranged from 93.8 to 108.1%. The method was successfully applied in a pharmacokinetic study of vindoline and catharanthine in rats. The bioavailability of vindoline and catharanthine were 5.4 and 4.7%, respectively. Copyright © 2014 John Wiley & Sons, Ltd.     

Metabolic profiles of dioscin in rats revealed by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry

Dioscin (DIS), one of the most abundant bioactive steroidal saponins in Dioscorea sp., is used as a complementary medicine to treat coronary disease and angina pectoris in China. Although the pharmacological activities and pharmacokinetics of DIS have been well demonstrated, information regarding the final metabolic fates is very limited. This study investigated the in vivo metabolic profiles of DIS after oral administration by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry method. The structures of the metabolites were identified and tentatively characterized by means of comparing the molecular mass, retention time and fragmentation pattern of the analytes with those of the parent compound. A total of eight metabolites, including seven phase I and one phase II metabolites, were detected and tentatively identified for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. In addition, a possible metabolic pathway on the biotransformation of DIS in vivo was proposed. This study provides valuable and new information on the metabolism of DIS, which will be helpful for further understanding its mechanism of action. Copyright © 2015 John Wiley & Sons, Ltd.     

The Effect of the Spacer of Bis(biurea) Ligands on the Structure of A2L3‐type (A=anion) Phosphate Complexes

By tuning the length and rigidity of the spacer of bis(biurea) ligands L, three structural motifs of the A₂L₃ complexes (A represents anion, here orthophosphate PO₄^3?), namely helicate, mesocate, and mono‐bridged motif, have been assembled by coordination of the ligand to phosphate anion. Crystal structure analysis indicated that in the three complexes, each of the phosphate ions is coordinated by twelve hydrogen bonds from six surrounding urea groups. The anion coordination properties in solution have also been studied. The results further demonstrate the coordination behavior of phosphate ion, which shows strong tendency for coordination saturation and geometrical preference, thus allowing for the assembly of novel anion coordination‐based structures as in transition‐metal complexes.