Suchergebnisse

The Nobi plain underlain by younger sediments is situated in the central part of Japan and is about 1300 km^2 in area. The yearly rates of subsidence in this area were 1.4-1.8 mm before 1925, 2-5 mm during the period from 1925 to 1950, 10-20 mm during the period from 1950 to 1960, 20-40 mm during the period from 1960 to 1965 and more than 100 mm at places having severe subsidence recently. The major cause of this increasing subsidence is the increasing withdrawal of ground water for industrial, agricultural and other purposes. As a result of such subsidence, an area of 250 km^2 subsided below the mean sea level. The drainage during and after heavy rainfalls has been becoming difficult day by day, and the potential danger' of tidal flood under a typhoon has been increasing year by year. Against such subsidence of the Nobi plain, investigations are being done by officials of central and prefectural governments and professors of universities in this area. Based on the investigations, withdrawal of ground water in this plain is now being controlled by regulations of the authorities concerned.

BackgroundRilpivirine (TMC‐278) is a second‐generation NNRTI that is highly potent against both wild‐type and drug‐resistant HIV‐1 strains. The quantification of rilpivirine in human plasma is important to support clinical studies and determine pharmacokinetic parameters of rilpivirine. Until now there has been a methodological report for the determination of rilpivirine using LC‐MS/MS. However, the MS‐MS detector needs to be delicately set and it is expensive. To bypass these difficulties, we aimed to develop more conventional procedures for determining rilpivirine plasma concentration by LC‐MS method.MethodsA Waters Alliance 2695 HPLC and a Micromass ZQ‐2000 MS, controlled with MassLynx version 4.0 software, were used for detection. Our method involves rapid liquid‐liquid drug extraction from plasma and use of gradient elution on a reversed‐phase C18 column. The mobile phase comprised 0.1 mM EDTA in 0.1% acetic acid (65%), acetonitrile (15%), and methanol (20%). Quantitative analysis detected rilpivirine at m/z 367, and the internal standard, at m/z 313, all in the form of ions.ResultsThe established LC‐MS method was validated by estimating the precision and accuracy for inter‐ and intraday analysis in the concentration range of 18–715 ng/ml. The calibration curve was linear in this range. Average accuracy ranged from 100.0 to 100.6%. Relative standard deviations of both inter‐ and intraday assays were less than 3.3%. Recovery of rilpivirine was more than 82.0%.ConclusionsOur newly developed LC‐MS method achieves the same level of reproducibility and accuracy as the LC‐MS/MS method. Our method provides a conventional, accurate and precise way to determine rilpivirine in human plasma. This method can be used in routine clinical application for HIV‐1 infected patients, and permits management of drug interactions and toxicity for rilpivirine.