Zhong W Z
Drug Metabolism Research, Upjohn Laboratories, Kalamazoo, MI 49001.
J Chromatogr. 1993 Jan 15;629(1):83-7. doi: 10.1016/0021-9673(93)80357-e.
The techniques of solid-phase extraction (SPE) were applied in the analytical method development for the determination of U-82217, 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-[(4-methoxyphenyl)methyl] -imidazo[1,5-a]quinoxalin-4(5H)-one, in rat serum, urine and brain. Samples of serum, urine or brain homogenate containing U-82217 were loaded on C18 SPE columns and eluted with acetonitrile (300 microliters). The prepared samples were analyzed by reversed-phase HPLC using an ODS column with a mobile phase of acetonitrile-water (45:55, v/v) containing 0.12% of acetic acid (pH 6.0 +/- 0.1). The UV absorbance of the column effluent was monitored at a wavelength of 318 nm. The absolute extraction recovery from serum, urine and brain samples was ca. 90%. Linear calibration graphs were obtained over the ranges 5 ng/ml-20 micrograms/ml (serum), 20 ng/ml-20 micrograms/ml (urine) and 50 ng/g-200 micrograms/g (brain). The intra- and inter-assay precision and accuracy were all found to be < 13% at the concentrations evaluated. The strategy in SPE development and the application of this method to the determination of U-82217 in rat serum and brain for a pharmacokinetic study are also discussed.
固相萃取（SPE）技术应用于大鼠血清、尿液和脑组织中U - 82217（3 -（5 - 环丙基 - 1,2,4 - 恶二唑 - 3 - 基）- 5 - [（4 - 甲氧基苯基）甲基] - 咪唑并[1,5 - a]喹喔啉 - 4（5H）- 酮）测定的分析方法开发。将含有U - 82217的血清、尿液或脑匀浆样品加载到C18 SPE柱上，并用乙腈（300微升）洗脱。制备的样品采用反相高效液相色谱法进行分析，使用ODS柱，流动相为含0.12%乙酸（pH 6.0±0.1）的乙腈 - 水（45:55，v/v）。在318 nm波长下监测柱流出物的紫外吸光度。血清、尿液和脑样品的绝对提取回收率约为90%。在5 ng/ml - 20 μg/ml（血清）、20 ng/ml - 20 μg/ml（尿液）和50 ng/g - 200 μg/g（脑）范围内获得了线性校准曲线。在所评估的浓度下，批内和批间精密度及准确度均<13%。还讨论了SPE开发策略以及该方法在大鼠血清和脑组织中U - 82217测定的药代动力学研究中的应用。
