Development of a HPLC-MS/MS method for the simultaneous determination of nifedipine and lidocaine in human plasma.

The method for simultaneous determination of nifedipine (NIF) and lidocaine (LID) in human plasma by one-step sample preparation has been developed for the first time. Due to the photosensitivity of nifedipine and its low plasma concentrations a precise and reliable method was required. The method involved liquid-liquid extraction (methyl tert-butyl ether, MTBE), and 10µL of the resulting sample was analyzed by HPLC-MS/MS. Chromatographic separation was achieved on an YMC-Triart C18 HPLC column (100×2.0mm; S-5µm 12nm). The mobile phase was methanol:water, 60:40 (v/v) and contained 0.15% acetic acid. The linearity of the method was established in the concentration ranges of 0.5-50ng/mL for NIF and 1.0-500ng/mL for LID. Photodestruction of NIF under ambient light was evaluated. The validated method was successfully applied to analyze human plasma samples after rectal application of the drug (1g) containing 2.0% LID and 0.3% NIF.

Design, synthesis and structure-activity studies of rhodanine derivatives as HIV-1 integrase inhibitors.

Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone (rhodanine)-containing compounds as IN inhibitors. Herein, we report the design, synthesis and docking studies of a series of novel rhodanine derivatives as IN inhibitors. All these compounds were further tested against human apurinic/apyrimidinic endonuclease 1 (APE1) to determine their selectivity. Two compounds showed significant cytotoxicity in a panel of human cancer cell lines. Taken together, our results show that rhodanines are a promising class of compounds for developing drugs with antiviral and anticancer properties.