Metabolomics and marker-based stability studies of methanol extract of seeds of Syzygium cumini L.

Though, herbal medicines are prone to deterioration upon storage due to their complex nature, but less attention has been paid to investigating stability of such products to assign shelf-life. Therefore, the present study aimed to assess the accelerated stability of methanolic extract of seeds of Syzygium cumini. The extract was kept at three different storage conditions (30oC/60% RH, 40oC/75% RH and 60oC/85% RH) for a period of 6 months. The samples withdrawn at 0 (before starting the study), 1, 2, 3, 4 and 6 months were analyzed to get UV-Visible metabolomics fingerprints and determine caffeic acid contents using RP-HPLC. The comparison of metabolomics fingerprints indicated that the extract was stable for 1 month at all the three storage conditions. However, caffeic acid contents were found to be intact for a longer period of time. Following the zero order degradation, caffeic acid was predicted to be stable for more than 3 years, if kept at 25oC. The results of the present study indicate that metabolomes of methanol extract of seeds of Syzygium cumini change very fast, suggesting the development of stable formulations.

Differential effects of ketoconazole and primaquine on the pharmacokinetics and tissue distribution of imatinib in mice.

Imatinib, a selective inhibitor of c-KIT and Bcr-Abl tyrosine kinases, approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors, shows further therapeutic potential for gliomas, glioblastoma, renal cell carcinoma, autoimmune nephritis and other neoplasms. It is metabolized by CYP3A4, is highly bound to alpha-1-acid glycoprotein and is a P-glycoprotein substrate limiting its brain distribution. We assess imatinib's protein binding interaction with primaquine, which also binds to alpha-1-acid glycoprotein, and its metabolic interaction with ketoconazole, which is a CYP3A4 inhibitor, on its pharmacokinetics and biodistribution. Male ICR mice, 9-12 weeks old were given imatinib PO (50 mg/kg) alone or co-administered with primaquine (12.5 mg/kg), ketoconazole (50 mg/kg) or both, and imatinib concentration in the plasma, kidney, liver and brain was measured at prescheduled time points by HPLC. Noncompartmental pharmacokinetic parameters were estimated. Primaquine increased 1.6-fold plasma AUC(0)--> infinity, C(Max) decreased 24%, T(Max) halved and t(1/2) and mean residence time were longer. Ketoconazole increased plasma AUC(0)-->infinity 64% and doubled the C(Max), but this dose did not affect t(1/2) or mean residence time. When ketoconazole and primaquine were co-administered, imatinib AUC(0)-->infinity and C(Max) increased 32 and 35%, respectively. Ketoconazole did not change imatinib's distribution efficiency in the liver and kidney, primaquine increased it two-fold and it was larger when both the drugs were co-administered with imatinib. Ketoconazole did not change brain penetration but primaquine increased it approximately three-fold. Ketoconazole and primaquine affect imatinib clearance, bioavailability and distribution pattern, which could improve the treatment of renal and brain tumors, but also increase toxicity. This would warrant hepatic and renal functions monitoring.