【摘要】 建立并评价了一种简单灵敏的方法测定狗血浆中PZS的含量.该方法利用HPLC-FLD结合乙醚萃取的前处理方法,采用C18色谱柱(150mm×4.6mm,5μm),流动相为30%乙腈和70%乙酸-乙酸钠缓冲液(pH=3.6),荧光检测器的激发波长为258nm,发射波长为387nm,在流动相流速为1.0mL/min时,其PZS和内标物的保留时间分别为4.4和5.8min.标准曲线在1.0～1000.0ng/mL的浓度范围内呈线性相关(r2>0.998),检出限为0.4ng/mL,标准曲线的日间变异系数低于5.0%,准确度在92.7%～104.2%范围内.在3d的分析质量控制研究中,日内和日间精密度均小于10%,准确度为95.9%～112.7%.该方法成功应用于一种新的口服制剂(PZS-磺丁基醚-β-环糊精包合物)的临床前期药代动力学评价,结果表明:该新型的包合药物具有缓释PZS的功效,且其相对生物利用率为105.0%.更多还原

【Abstract】 A simple and sensitive high performance liquid chromatography method using fluorescence detection(HPLCFLD) and a one-step single solvent extraction for the determination of prazosin(PZS) in dog plasma is developed and validated.After extraction with ether,the chromatographic separation of PZS is carried out using a reverse phase C18 column(150 mm×4.6 mm,5 μm) with a mobile phase of 30% acetonitrile and 70% acetic acid-sodium acetate buffer solution(pH = 3.6) and quantified by fluorescence detection operated with an excitation wavelength of 258 nm and an emission wavelength of 387 nm.The flow rate of the mobile phase is 1.0 mL /min and the retention time of PZS and the internal standard is found to be 4.4 and 5.8 min,respectively.The calibration curve is linear within a concentration range from 1.0 to 1 000.0 ng /mL(r2 > 0.998).The limit of detection is 0.4 ng /mL.The inter-day coefficient of variation(COV) of the calibration standards is below 5.0% and the mean accuracy is in the range from 92.7% to 104.2%.Moreover,by analyzing quality control plasma samples for three days,the results show that the method is precise and accurate,for the intra-and interday COV within 10% and the accuracy from 95.9% to 112.7%.The developed and validated method is successfully applied to pharmacokinetic study for the preclinical evaluation of a new peroral PZS-sulfobutyl ether beta-cyclodextrin(PZS-SBE-βCD) inclusion complex tablets(test preparation),which demonstrates that the test preparation released PZS is conducted in a slow and controlled way,and the relative bioavailability of the test preparation is found to be 105.0%.更多还原