JNJ-7706621 Inhibitor of the effect of recombinant human

sPLA2 nonpancreatic. Pharmacokinetics JNJ-7706621 of sPLA2 inhibitors female Wistar rats were used to monitor the clearance of sPLA2 inhibitor from the serum after intravenous administration. Anesthetized rats were treated with 5 mg kg 1 sPLA2 inhibitor injected in 70 dimethylformamide. Blood samples were collected from the tail vein at intervals over a period of 4 hours. Blood samples were then centrifuged to rperchen red Blutk And an aliquot of plasma in a clean R Hrchen and remove at 201C until analysis of the samples. To determine the concentration of inhibitor in plasma samples sPLA2, analyzing liquid chromatography-mass spectrometry was used. An internal standard was added to each sample.
The R Were Hrchen anges with an L Solution of 5 wv 1 citric Acid in water Acidified and extracted with dichloromethane HPLCgrade vortexing at full speed for 20 seconds. The R Hrchen centrifuged to facilitate the separation of the layers, has been removed, the lower layer and a new R Hrchen. The dichloromethane was. Using a centrifugal evaporator, and the residue in the mobile phase by vortexing for 20 s gel St and then End in a bottle Schchen autoinjector A set of Standardl solutions For generating a calibration curve is prepared by adding a Stamml Solution of the inhibitor and the internal standard at 5 mgmL one from an analog of the inhibitor prepared in 50 ml of plasma rat, briefly vortexed, and then extracted with dichloromethane as citric acid described above.
Samples on a PE Sciex API 3000 triple quadruple mass spectrometer with an Agilent 1100 HPLC were analyzed under isocratic conditions using a mobile phase consisting of acetonitrile 72, 27.9, and 0.1 water formic Ure equipped. Top-S molecules was a Phenomenex Luna C18, 5 mm, 100A ?, 50 with 2mm rate of 200 ml min-1, retention time: internal standard 2.4 min, 2.8 min sPLA2 inhibitor. Parent ions for sPLA2 inhibitor MHT 474 MHT 488 and the internal standard were fragmented ions produce both my 282, which were aligned in Q3. The data were smoothed TTET before integration and ambient ratio Ratio of drug to internal standard for quantification using a calibration curve with the commercial software used MacQuan 1.6. Model of intestinal injury IR adult Wistar rats weighing 200 250 g I female For 12 14 h before the experiment were born, but had free access to water.
The rats were on Sthesiert by intraperitoneal injection of 10 of a mixture of one and zolazepam tiletamine and 10 kg to 1 mg xylazine and normal K Body temperature is pla th mgkg rats maintained on a heating pad. The belly was a midline incision, the superior mesenteric artery, the main source of blood in the small intestine it set Opened. IR was in intestinal pla ant an occlusive device nontraumatic artery for 30 min isch Mix phase, by removing the clamp to the reperfusion of blood for 150 minutes carried out, followed erm Aligned. 15 min before occlusion of the right femoral vein was isolated and injected with either 5 mg kg JNJ-7706621 chemical structure

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