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摘要
In the present study, a specific and sensitive liquid chromatography-triple quadrupole mass spectrometry method was developed and validated for the determination of SP-141, a novel pyrido[b]indole anticancer agent. After a liquid-liquid extraction with n-hexane-dichloromethane-2-propanol (20:10:1, v/v/v) mixture, the analyte was separated on a Kinetex C-18 column (50 x 2.1 mm, 2.6 mu m) with mobile phases comprising of water (0.1% formic acid, v/v) and acetonitrile (0.1% formic acid, v/v) at a flow rate of 0.4 mL/min. The test compound (SP-141) and the internal standard (SP-157) were analyzed in the multiple reaction-monitoring mode using the mass transitions m/z 325.1 -%26gt; 282.0. The method was linear in the concentration range of 0.648-162 ng/mL with coefficients of determination (R-2) of 0.999 in mouse plasma. The lower limit of quantification was 0.648 ng/mL. The intra- and inter-day assay precisions (coefficient of variation, %CV) were less than 4.2% and accuracies (relative error, %RE) ranged from -6.1% to 2.1%. The extraction recoveries were between 97.1 and 103.1% and the relative matrix effect was minimal. In addition, SP-141 was found to be stable in the plasma after three freeze-thaw cycles, at 37 degrees C and 4 degrees C for 24 h, and at -80 degrees C for 4 weeks. It was also stable in the stock solution at room temperature for 24 h and after preparation in the autosampler for 36 h. The validated method was successfully applied to an initial pharmacokinetic study of SP-141 in CD-1 mice following intraperitoneal and intravenous administrations.
- 出版日期2014-10-15
